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EcoSal Plus

Domain 8:

Pathogenesis

Adaptive Immune Responses during Infection

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  • Authors: Lisa A. Cummings1, Brooke L. Deatherage2, and Brad T. Cookson3
  • Editor: Michael S. Donnenberg4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Laboratory Medicine and Department of Microbiology, University of Washington, Seattle, WA 98195; 2: Department of Laboratory Medicine and Department of Microbiology, University of Washington, Seattle, WA 98195; 3: Department of Laboratory Medicine and Department of Microbiology, University of Washington, Seattle, WA 98195; 4: University of Maryland, School of Medicine, Baltimore, MD
  • Received 21 August 2008 Accepted 17 November 2008 Published 17 September 2009
  • Address correspondence to Brad T. Cookson cookson@u.washington.edu.
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  • Abstract:

    The interaction between and its host is complex and dynamic: the host mounts an immune defense against the pathogen, which in turn acts to reduce, evade, or exploit these responses to successfully colonize the host. Although the exact mechanisms mediating protective immunity are poorly understood, it is known that T cells are a critical component of immunity to infection, and a robust T-cell response is required for both clearance of primary infection and resistance to subsequent challenge. B-cell functions, including but not limited to antibody production, are also required for generation of protective immunity. Additionally, interactions among host cells are essential. For example, antigen-presenting cells (including B cells) express cytokines that participate in CD4+ T cell activation and differentiation. Differentiated CD4+ T cells secrete cytokines that have both autocrine and paracrine functions, including recruitment and activation of phagocytes, and stimulation of B cell isotype class switching and affinity maturation. Multiple bacterium-directed mechanisms, including altered antigen expression and bioavailability and interference with antigen-presenting cell activation and function, combine to modify "pathogenic signature" in order to minimize its susceptibility to host immune surveillance. Therefore, a more complete understanding of adaptive immune responses may provide insights into pathogenic bacterial functions. Continued identification of adaptive immune targets will guide rational vaccine development, provide insights into host functions required to resist infection, and correspondingly provide valuable reagents for defining the critical pathogenic capabilities of that contribute to their success in causing acute and chronic infections.

  • Citation: Cummings L, Deatherage B, Cookson B. 2009. Adaptive Immune Responses during Infection, EcoSal Plus 2009; doi:10.1128/ecosalplus.8.8.11

Key Concept Ranking

Tumor Necrosis Factor alpha
0.40770218
Outer Membrane Proteins
0.347802
Bacterial Proteins
0.3406962
0.40770218

References

1. Wright A, Semple D. 1897. Remarks on vacinnation against typhoid fever. BMJ 1:256. [CrossRef]
2. Hobson D. 1957. Resistance to reinfection in experimental mouse typhoid. J Hyg 55:334–343. [PubMed][CrossRef]
3. Collins FM, Mackaness GB. 1968. Delayed hypersensitivity and arthus reactivity in relation to host resistance in Salmonella-infected mice. J Immunol 101:830–845. [PubMed]
4. Killar LM, Eisenstein TK. 1985. Immunity to Salmonella typhimurium infection in C3H/HeJ and C3H/HeNCrlBR mice: studies with an aromatic-dependent live S. typhimurium strain as a vaccine. Infect Immun 47:605–612. [PubMed]
5. Kotlarski I, Pope M, Doherty K, Attridge SR. 1989. The in vitro proliferative response of lymphoid cells of mice infected with Salmonella enteritidis 11RX. Immunol Cell Biol 67(Pt 1):19–29. [PubMed][CrossRef]
6. Ushiba D. 1965. Two types of immunity in experimental typhoid: “cellular immunity” and “humoral immunity.” Keio J Med 14:45–61. [PubMed]
7. Mastroeni P, Villarreal-Ramos B, Hormaeche CE. 1993. Adoptive transfer of immunity to oral challenge with virulent Salmonellae in innately susceptible BALB/c mice requires both immune serum and T cells. Infect Immun 61:3981–3984. [PubMed]
8. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P. 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2:361–367. [PubMed][CrossRef]
9. Vazquez-Torres A, Jones-Carson J, Baumler AJ, Falkow S, Valdivia R, Brown W, Le M, Berggren R, Parks WT, Fang FC. 1999. Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature 401:804–808. [PubMed][CrossRef]
10. Richter-Dahlfors A, Buchan AM, Finlay BB. 1997. Murine salmonellosis studied by confocal microscopy: Salmonella typhimurium resides intracellularly inside macrophages and exerts a cytotoxic effect on phagocytes in vivo. J Exp Med 186:569–580. [PubMed][CrossRef]
11. Salcedo SP, Noursadeghi M, Cohen J, Holden DW. 2001. Intracellular replication of Salmonella typhimurium strains in specific subsets of splenic macrophages in vivo. Cell Microbiol 3:587–597. [PubMed][CrossRef]
12. Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, Lepak NM, Johnson LL, Swain SL, Lund FE. 2000. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 1:475–482. [PubMed][CrossRef]
13. Janeway CA, Travers P, Walport M, Shlomchik M. 2001. Immunobiology: the Immune System in Health and Disease, 5th ed. Garland Publishing, New York, NY.
14. Fields PI, Swanson RV, Haidaris CG, Heffron F. 1986. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci USA 83:5189–5193. [PubMed][CrossRef]
15. Rydstrom A, Wick MJ. 2007. Monocyte recruitment, activation, and function in the gut-associated lymphoid tissue during oral Salmonella infection. J Immunol 178:5789–5801. [PubMed]
16. Brennan MA, Cookson BT. 2000. Salmonella induces macrophage death by caspase-1-dependent necrosis. Mol Microbiol 38:31–40. [PubMed][CrossRef]
17. Fink SL, Cookson BT. 2007. Pyroptosis and host cell death responses during Salmonella infection. Cell Microbiol 9:2562–2570. [PubMed][CrossRef]
18. van der Velden AW, Velasquez M, Starnbach MN. 2003. Salmonella rapidly kill dendritic cells via a caspase-1-dependent mechanism. J Immunol 171:6742–6749. [PubMed]
19. Levine MM, Black RE, Lanata C. 1982. Precise estimation of the numbers of chronic carriers of Salmonella typhi in Santiago, Chile, an endemic area. J Infect Dis 146:724–726. [PubMed]
20. Monack DM, Bouley DM, Falkow S. 2004. Salmonella typhimurium persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp1+/+ mice and can be reactivated by IFNgamma neutralization. J Exp Med 199:231–241. [PubMed][CrossRef]
21. Fieschi C, Dupuis S, Catherinot E, Feinberg J, Bustamante J, Breiman A, Altare F, Baretto R, Le Deist F, Kayal S, Koch H, Richter D, Brezina M, Aksu G, Wood P, Al-Jumaah S, Raspall M, Da Silva Duarte AJ, Tuerlinckx D, Virelizier JL, Fischer A, Enright A, Bernhoft J, Cleary AM, Vermylen C, Rodriguez-Gallego C, Davies G, Blutters-Sawatzki R, Siegrist CA, Ehlayel MS, Novelli V, Haas WH, Levy J, Freihorst J, Al-Hajjar S, Nadal D, De Moraes Vasconcelos D, Jeppsson O, Kutukculer N, Frecerova K, Caragol I, Lammas D, Kumararatne DS, Abel L, Casanova JL. 2003. Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications. J Exp. Med. 197:527–535. [PubMed][CrossRef]
22. MacLennan C, Fieschi C, Lammas DA, Picard C, Dorman SE, Sanal O, MacLennan JM, Holland SM, Ottenhoff TH, Casanova JL, Kumararatne DS. 2004. Interleukin (IL)-12 and IL-23 are key cytokines for immunity against Salmonella in humans. J Infect. Dis. 190:1755–1757. [PubMed][CrossRef]
23. Gordon MA, Banda HT, Gondwe M, Gordon SB, Boeree MJ, Walsh AL, Corkill JE, Hart CA, Gilks CF, Molyneux ME. 2002. Non-typhoidal Salmonella bacteraemia among HIV-infected Malawian adults: high mortality and frequent recrudescence. AIDS 16:1633–1641. [PubMed][CrossRef]
24. Pang T, Bhutta ZA, Finlay BB, Altwegg M. 1995. Typhoid fever and other salmonellosis: a continuing challenge. Trends Microbiol 3:253–255. [PubMed][CrossRef]
25. Hayes C, Lyons RA, Warde C. 1991. A large outbreak of salmonellosis and its economic cost. Isr Med J 84:65–66. [PubMed]
26. Rubino JR. 1997. The economic impact of human Salmonella infection. Clin Microbiol Newslett 19:25–29. [CrossRef]
27. Ugrinovic S, Menager N, Goh N, Mastroeni P. 2003. Characterization and development of T-cell immune responses in B-cell-deficient [Igh-6(−/−)] mice with Salmonella enterica serovar Typhimurium infection. Infect Immun 71:6808–6819. [PubMed][CrossRef]
28. Kalupahana RS, Mastroeni P, Maskell D, Blacklaws BA. 2005. Activation of murine dendritic cells and macrophages induced by Salmonella enterica serovar Typhimurium. Immunology 115:462–472. [PubMed][CrossRef]
29. Pietila TE, Veckman V, Kyllonen P, Lahteenmaki K, Korhonen TK, Julkunen I. 2005. Activation, cytokine production, and intracellular survival of bacteria in Salmonella-infected human monocyte-derived macrophages and dendritic cells. J Leukoc Biol 78:909–920. [PubMed][CrossRef]
30. Zhao C, Wood MW, Galyov EE, Hopken UE, Lipp M, Bodmer HC, Tough DF, Carter RW. 2006. Salmonella typhimurium infection triggers dendritic cells and macrophages to adopt distinct migration patterns in vivo. Eur J Immunol 36:2939–2950. [PubMed][CrossRef]
31. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. 2000. Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811. [PubMed][CrossRef]
32. Geissmann F, Auffray C, Palframan R, Wirrig C, Ciocca A, Campisi L, Narni-Mancinelli E, Lauvau G. 2008. Blood monocytes: distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T-cell responses. Immunol Cell Biol 86:398–408. [PubMed][CrossRef]
33. Sundquist M, Wick MJ. 2005. TNF-alpha-dependent and -independent maturation of dendritic cells and recruited CD11c(int)CD11b+ cells during oral Salmonella infection. J Immunol 175:3287–3298. [PubMed]
34. Wick MJ. 2007. Monocyte and dendritic cell recruitment and activation during oral Salmonella infection. Immunol Lett 112:68–74. [PubMed][CrossRef]
35. Pozzi LA, Maciaszek JW, Rock KL. 2005. Both dendritic cells and macrophages can stimulate naive CD8 T cells in vivo to proliferate, develop effector function, and differentiate into memory cells. J Immunol 175:2071–2081. [PubMed]
36. Niedergang F, Sirard JC, Blanc CT, Kraehenbuhl JP. 2000. Entry and survival of Salmonella typhimurium in dendritic cells and presentation of recombinant antigens do not require macrophage-specific virulence factors. Proc Natl Acad Sci USA 97:14650–14655. [PubMed][CrossRef]
37. Jantsch J, Cheminay C, Chakravortty D, Lindig T, Hein J, Hensel M. 2003. Intracellular activities of Salmonella enterica in murine dendritic cells. Cell Microbiol 5:933–945. [PubMed][CrossRef]
38. Delamarre L, Pack M, Chang H, Mellman I, Trombetta ES. 2005. Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science 307:1630–1634. [PubMed][CrossRef]
39. Hopkins SA, Niedergang F, Corthesy-Theulaz IE, Kraehenbuhl JP. 2000. A recombinant Salmonella typhimurium vaccine strain is taken up and survives within murine Peyer's patch dendritic cells. Cell Microbiol 2:59–68. [PubMed][CrossRef]
40. Cheminay C, Mohlenbrink A, Hensel M. 2005. Intracellular Salmonella inhibit antigen presentation by dendritic cells. J Immunol 174:2892–2899. [PubMed]
41. Salazar-Gonzalez RM, Niess JH, Zammit DJ, Ravindran R, Srinivasan A, Maxwell JR, Stoklasek T, Yadav R, Williams IR, Gu X, McCormick BA, Pazos MA, Vella AT, Lefrancois L, Reinecker HC, McSorley SJ. 2006. CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches. Immunity 24:623–632. [PubMed][CrossRef]
42. Yrlid U, Svensson M, Hakansson A, Chambers BJ, Ljunggren HG, Wick MJ. 2001. In vivo activation of dendritic cells and T cells during Salmonella enterica serovar Typhimurium infection. Infect Immun 69:5726–5735. [PubMed][CrossRef]
43. Cookson BT, Bevan MJ. 1997. Identification of a natural T cell epitope presented by Salmonella-infected macrophages and recognized by T cells from orally immunized mice. J Immunol 158:4310–4319. [PubMed]
44. Martin-Orozco N, Isibasi A, Ortiz-Navarrete V. 2001. Macrophages present exogenous antigens by class I major histocompatibility complex molecules via a secretory pathway as a consequence of interferon-gamma activation. Immunology 103:41–48. [PubMed][CrossRef]
45. Wick MJ, Harding CV, Twesten NJ, Normark SJ, Pfeifer JD. 1995. The phoP locus influences processing and presentation of Salmonella typhimurium antigens by activated macrophages. Mol Microbiol 16:465–476. [PubMed][CrossRef]
46. Wijburg OL, Van Rooijen N, Strugnell RA. 2002. Induction of CD8+ T lymphocytes by Salmonella typhimurium is independent of Salmonella pathogenicity island 1-mediated host cell death. J Immunol 169:3275–3283. [PubMed]
47. Wijburg OL, Simmons CP, van Rooijen N, Strugnell RA. 2000. Dual role for macrophages in vivo in pathogenesis and control of murine Salmonella enterica var. Typhimurium infections. Eur J Immunol 30:944–953. [PubMed][CrossRef]
48. Bueno SM, Gonzalez PA, Schwebach JR, Kalergis AM. 2007. T cell immunity evasion by virulent Salmonella enterica. Immunol Lett 111:14–20. [PubMed][CrossRef]
49. Tobar JA, Carreno LJ, Bueno SM, Gonzalez PA, Mora JE, Quezada SA, Kalergis AM. 2006. Virulent Salmonella enterica serovar typhimurium evades adaptive immunity by preventing dendritic cells from activating T cells. Infect Immun 74:6438–6448. [PubMed][CrossRef]
50. Alaniz RC, Cummings LA, Bergman MA, Rassoulian-Barrett SL, Cookson BT. 2006. Salmonella typhimurium coordinately regulates FliC location and reduces dendritic cell activation and antigen presentation to CD4+ T cells. J Immunol 177:3983–3993. [PubMed]
51. Cummings LA, Wilkerson WD, Bergsbaken T, Cookson BT. 2006. In vivo, fliC expression by Salmonella enterica serovar Typhimurium is heterogeneous, regulated by ClpX, and anatomically restricted. Mol Microbiol 61:795–809. [PubMed][CrossRef]
52. Cummings LA, Barrett SL, Wilkerson WD, Fellnerova I, Cookson BT. 2005. FliC-specific CD4+ T cell responses are restricted by bacterial regulation of antigen expression. J Immunol 174:7929–7938. [PubMed]
53. Alpuche Aranda CM, Swanson JA, Loomis WP, Miller SI. 1992. Salmonella typhimurium activates virulence gene transcription within acidified macrophage phagosomes. Proc Natl Acad Sci USA 89:10079–10083. [PubMed][CrossRef]
54. Groisman EA. 2001. The pleiotropic two-component regulatory system PhoP-PhoQ. J Bacteriol 183:1835–1842. [PubMed][CrossRef]
55. Ernst RK, Guina T, Miller SI. 1999. How intracellular bacteria survive: surface modifications that promote resistance to host innate immune responses. J Infect Dis 179(Suppl. 2):S326–S330. [PubMed][CrossRef]
56. Gunn JS. 2001. Bacterial modification of LPS and resistance to antimicrobial peptides. J Endotoxin Res 7:57–62. [PubMed][CrossRef]
57. Kawasaki K, Ernst RK, Miller SI. 2004. 3-O-deacylation of lipid A by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4. J Biol Chem 279:20044–20048. [PubMed][CrossRef]
58. Murata T, Tseng W, Guina T, Miller SI, Nikaido H. 2007. PhoPQ-mediated regulation produces a more robust permeability barrier in the outer membrane of Salmonella enterica serovar typhimurium. J Bacteriol 189:7213–7222. [PubMed][CrossRef]
59. Bergman MA, Cummings LA, Barrett SL, Smith KD, Lara JC, Aderem A, Cookson BT. 2005. CD4+ T cells and toll-like receptors recognize Salmonella antigens expressed in bacterial surface organelles. Infect Immun 73:1350–1356. [PubMed][CrossRef]
60. Fink SL, Bergsbaken T, Cookson BT. 2008. Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms. Proc Natl Acad Sci USA 105:4312–4317. [PubMed][CrossRef]
61. Eguchi M, Sekiya Y, Kikuchi Y, Takaya A, Yamamoto T, Matsui H. 2007. Expressed Salmonella antigens within macrophages enhance the proliferation of CD4+ and CD8+ T lymphocytes by means of bystander dendritic cells. FEMS Immunol Med Microbiol 50:411–420. [PubMed][CrossRef]
62. Yrlid U, Wick MJ. 2000. Salmonella-induced apoptosis of infected macrophages results in presentation of a bacteria-encoded antigen after uptake by bystander dendritic cells. J Exp Med 191:613–624. [PubMed][CrossRef]
63. Tobar JA, Gonzalez PA, Kalergis AM. 2004. Salmonella escape from antigen presentation can be overcome by targeting bacteria to Fc gamma receptors on dendritic cells. J Immunol 173:4058–4065. [PubMed]
64. Bueno SM, Gonzalez PA, Carreno LJ, Tobar JA, Mora GC, Pereda CJ, Salazar-Onfray F, Kalergis AM. 2008. The capacity of Salmonella to survive inside dendritic cells and prevent antigen presentation to T cells is host specific. Immunology 124:522–533. [PubMed][CrossRef]
65. van der Velden AW, Copass MK, Starnbach MN. 2005. Salmonella inhibit T cell proliferation by a direct, contact-dependent immunosuppressive effect. Proc Natl Acad Sci USA 102:17769–17774. [PubMed][CrossRef]
66. van der Velden AW, Dougherty JT, Starnbach MN. 2008. Down-modulation of TCR expression by Salmonella enterica serovar Typhimurium. J Immunol 180:5569–5574. [PubMed]
67. Hess J, Ladel C, Miko D, Kaufmann SH. 1996. Salmonella typhimurium aroA− infection in gene-targeted immunodeficient mice: major role of CD4+ TCR-alpha beta cells and IFN-gamma in bacterial clearance independent of intracellular location. J Immunol 156:3321–3326. [PubMed]
68. Mastroeni P, Villarreal RB, Hormaeche CE. 1992. Role of T cells, TNF alpha and IFN gamma in recall of immunity to oral challenge with virulent Salmonellae in mice vaccinated with live attenuated aro-Salmonella vaccines. Microb Pathog 13:477–491. [PubMed][CrossRef]
69. Nauciel C. 1990. Role of CD4+ T cells and T-independent mechanisms in acquired resistance to Salmonella typhimurium infection. J Immunol 145:1265–1269. [PubMed]
70. Weintraub BC, Eckmann L, Okamoto S, Hense M, Hedrick SM, Fierer J. 1997. Role of alphabeta and gammadelta T cells in the host response to Salmonella infection as demonstrated in T-cell-receptor-deficient mice of defined Ity genotypes. Infect Immun 65:2306–2312. [PubMed]
71. Bettelli E, Korn T, Kuchroo VK. 2007. Th17: the third member of the effector T cell trilogy. Curr Opin Immunol 19:652–657. [PubMed][CrossRef]
72. Harrington LE, Mangan PR, Weaver CT. 2006. Expanding the effector CD4 T-cell repertoire: the Th17 lineage. Curr Opin Immunol 18:349–356. [PubMed][CrossRef]
73. Korn T, Oukka M, Kuchroo V, Bettelli E. 2007. Th17 cells: effector T cells with inflammatory properties. Semin Immunol 19:362–371. [PubMed]
74. Weaver CT, Hatton RD, Mangan PR, Harrington LE. 2007. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 25:821–852. [PubMed][CrossRef]
75. Hayday AC. 2000. [gamma][delta] cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol 18:975–1026. [PubMed][CrossRef]
76. Ravindran R, McSorley SJ. 2005. Tracking the dynamics of T-cell activation in response to Salmonella infection. Immunology 114:450–458. [PubMed][CrossRef]
77. Kirby AC, Sundquist M, Wick MJ. 2004. In vivo compartmentalization of functionally distinct, rapidly responsive antigen-specific T-cell populations in DNA-immunized or Salmonella enterica serovar Typhimurium-infected mice. Infect Immun 72:6390–6400. [PubMed]
78. Lo WF, Ong H, Metcalf ES, Soloski MJ. 1999. T cell responses to Gram-negative intracellular bacterial pathogens: a role for CD8+ T cells in immunity to Salmonella infection and the involvement of MHC class Ib molecules. J Immunol 162:5398–5406. [PubMed]
79. Mittrucker HW, Kohler A, Kaufmann SH. 2002. Characterization of the murine T-lymphocyte response to Salmonella enterica serovar Typhimurium infection. Infect Immun 70:199–203. [PubMed][CrossRef]
80. Lundin BS, Johansson C, Svennerholm AM. 2002. Oral immunization with a Salmonella enterica serovar typhi vaccine induces specific circulating mucosa-homing CD4(+) and CD8(+) T cells in humans. Infect Immun 70:5622–5627. [PubMed][CrossRef]
81. Salerno-Goncalves R, Fernandez-Vina M, Lewinsohn DM, Sztein MB. 2004. Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. J Immunol 173:5852–5862. [PubMed]
82. Salerno-Goncalves R, Pasetti MF, Sztein MB. 2002. Characterization of CD8(+) effector T cell responses in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. J Immunol 169:2196–2203. [PubMed]
83. Salerno-Goncalves R, Wyant TL, Pasetti MF, Fernandez-Vina M, Tacket CO, Levine MM, Sztein MB. 2003. Concomitant induction of CD4+ and CD8+ T cell responses in volunteers immunized with Salmonella enterica serovar typhi strain CVD 908-htrA. J Immunol 170:2734–2741. [PubMed]
84. Sztein MB, Tanner MK, Polotsky Y, Orenstein JM, Levine MM. 1995. Cytotoxic T lymphocytes after oral immunization with attenuated vaccine strains of Salmonella typhi in humans. J Immunol 155:3987–3993. [PubMed]
85. Bumann D. 2001. In vivo visualization of bacterial colonization, antigen expression, and specific T-cell induction following oral administration of live recombinant Salmonella enterica serovar Typhimurium. Infect Immun 69:4618–4626. [PubMed][CrossRef]
86. McSorley SJ, Asch S, Costalonga M, Reinhardt RL, Jenkins MK. 2002. Tracking Salmonella-specific CD4 T cells in vivo reveals a local mucosal response to a disseminated infection. Immunity 16:365–377. [PubMed][CrossRef]
87. Davies A, Lopez-Briones S, Ong H, O’Neil-Marshall C, Lemonnier FA, Nagaraju K, Metcalf ES, Soloski MJ. 2004. Infection-induced expansion of a MHC Class Ib-dependent intestinal intraepithelial gammadelta T cell subset. J Immunol 172:6828–6837. [PubMed]
88. Mixter PF, Camerini V, Stone BJ, Miller VL, Kronenberg M. 1994. Mouse T lymphocytes that express a gamma delta T-cell antigen receptor contribute to resistance to Salmonella infection in vivo. Infect Immun 62:4618–4621. [PubMed]
89. Sinha K, Mastroeni P, Harrison J, de Hormaeche RD, Hormaeche CE. 1997. Salmonella typhimurium aroA, htrA, and aroD htrA mutants cause progressive infections in athymic (nu/nu) BALB/c mice. Infect Immun 65:1566–1569. [PubMed]
90. Hormaeche CE, Mastroeni P, Arena A, Uddin J, Joysey HS. 1990. T cells do not mediate the initial suppression of a Salmonella infection in the RES. Immunology 70:247–250. [PubMed]
91. Paul C, Shalala K, Warren R, Smith R. 1985. Adoptive transfer of murine host protection to salmonellosis with T-cell growth factor-dependent, Salmonella-specific T-cell lines. Infect Immun 48:40–43. [PubMed]
92. Paul CC, Norris K, Warren R, Smith RA. 1988. Transfer of murine host protection by using interleukin-2-dependent T-lymphocyte lines. Infect Immun 56:2189–2192. [PubMed]
93. Centers for Disease Control Prevention. 1992. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recommend Rep 41:1–19. [PubMed]
94. Grant AD, Sidibe K, Domoua K, Bonard D, Sylla-Koko F, Dosso M, Yapi A, Maurice C, Whitaker JP, Lucas SB, Hayes RJ, Wiktor SZ, De Cock KM, Greenberg AE. 1998. Spectrum of disease among HIV-infected adults hospitalised in a respiratory medicine unit in Abidjan, Cote d’Ivoire. Int. J Tuberc. Lung Dis. 2:926–934. [PubMed]
95. Hohmann EL. 2001. Nontyphoidal salmonellosis. Clin Infect Dis 32:263–269. [PubMed][CrossRef]
96. Hung CC, Hung MN, Hsueh PR, Chang SY, Chen MY, Hsieh SM, Sheng WH, Sun HY, Huang YT, Lo YC, Hsiao CF, Chang SC. 2007. Risk of recurrent nontyphoid Salmonella bacteremia in HIV-infected patients in the era of highly active antiretroviral therapy and an increasing trend of fluoroquinolone resistance. Clin Infect Dis 45:e60–e67. [PubMed][CrossRef]
97. Kankwatira AM, Mwafulirwa GA, Gordon MA. 2004. Non-typhoidal Salmonella bacteraemia—an under-recognized feature of AIDS in African adults. Trop Doct 34:198–200. [PubMed]
98. Nelson MR, Shanson DC, Hawkins DA, Gazzard BG. 1992. Salmonella, Campylobacter and Shigella in HIV-seropositive patients. AIDS 6:1495–1498. [PubMed][CrossRef]
99. Glaser JB, Morton-Kute L, Berger SR, Weber J, Siegal FP, Lopez C, Robbins W, Landesman SH. 1985. Recurrent Salmonella typhimurium bacteremia associated with the acquired immunodeficiency syndrome. Ann Intern Med 102:189–193. [PubMed]
100. van Diepen A, Koudijs JSvan de Gevel MM, Ossendorp F, Beekhuizen H, Janssen R, JTvan Dissel. 2005. Gamma irradiation or CD4+-T-cell depletion causes reactivation of latent Salmonella enterica serovar Typhimurium infection in C3H/HeN mice. Infect. Immun. 73:2857–2862. [PubMed][CrossRef]
101. Soloski MJ, Metcalf ES. 2001. The involvement of class Ib molecules in the host response to infection with Salmonella and its relevance to autoimmunity. Microbes Infect 3:1249–1259. [PubMed][CrossRef]
102. Ugrinovic S, Brooks CG, Robson J, Blacklaws BA, Hormaeche CE, Robinson JH. 2005. H2–M3 major histocompatibility complex class Ib-restricted CD8 T cells induced by Salmonella enterica serovar Typhimurium infection recognize proteins released by Salmonella serovar Typhimurium. Infect Immun 73:8002–8008. [PubMed][CrossRef]
103. Bao S, Beagley KW, France MP, Shen J, Husband AJ. 2000. Interferon-gamma plays a critical role in intestinal immunity against Salmonella typhimurium infection. Immunology 99:464–472. [PubMed][CrossRef]
104. Mastroeni P, Villarreal-Ramos B, Hormaeche CE. 1993. Effect of late administration of anti-TNF alpha antibodies on a Salmonella infection in the mouse model. Microb Pathog 14:473–480. [PubMed]
105. Muotiala A, Makela PH. 1993. Role of gamma interferon in late stages of murine salmonellosis. Infect Immun 61:4248–4253. [PubMed]
106. Nauciel C, Espinasse-Maes F. 1992. Role of gamma interferon and tumor necrosis factor alpha in resistance to Salmonella typhimurium infection. Infect Immun 60:450–454. [PubMed]
107. Ravindran R, Foley J, Stoklasek T, Glimcher LH, McSorley SJ. 2005. Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection. J Immunol 175:4603–4610. [PubMed]
108. Fernandez-Cabezudo MJ, Ali SA, Ullah A, Hasan MY, Kosanovic M, Fahim MA, Adem A, al-Ramadi BK. 2007. Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses. Toxicol Appl Pharmacol 218:215–226. [PubMed][CrossRef]
109. Ramarathinam L, Shaban RA, Niesel DW, Klimpel GR. 1991. Interferon gamma (IFN-gamma) production by gut-associated lymphoid tissue and spleen following oral Salmonella typhimurium challenge. Microb Pathog 11:347–356. [PubMed][CrossRef]
110. Mora JR, Bono MR, Manjunath N, Weninger W, Cavanagh LL, Rosemblatt M, Von Andrian UH. 2003. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 424:88–93. [PubMed][CrossRef]
111. Mastroeni P. 2002. Immunity to systemic Salmonella infections. Curr Mol Med 2:393–406. [PubMed][CrossRef]
112. Price JD, Simpfendorfer KR, Mantena RR, Holden J, Heath WR, van Rooijen N, Strugnell RA, Wijburg OL. 2007. Gamma interferon-independent effects of interleukin-12 on immunity to Salmonella enterica serovar Typhimurium. Infect Immun 75:5753–5762. [PubMed][CrossRef]
113. Ramarathinam L, Niesel DW, Klimpel GR. 1993. Salmonella typhimurium induces IFN-gamma production in murine splenocytes. Role of natural killer cells and macrophages. J Immunol 150:3973–3981. [PubMed]
114. Shedlock DJ, Shen H. 2003. Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 300:337–339. [PubMed][CrossRef]
115. Sun JC, Williams MA, Bevan MJ. 2004. CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection. Nat Immunol 5:927–933. [PubMed][CrossRef]
116. Luu RA, Gurnani K, Dudani R, Kammara R, van Faassen H, Sirard JC, Krishnan L, Sad S. 2006. Delayed expansion and contraction of CD8+ T cell response during infection with virulent Salmonella typhimurium. J Immunol 177:1516–1525. [PubMed]
117. Stenger S, Hanson DA, Teitelbaum R, Dewan P, Niazi KR, Froelich CJ, Ganz T, Thoma-Uszynski S, Melian A, Bogdan C, Porcelli SA, Bloom BR, Krensky AM, Modlin RL. 1998. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282:121–125. [PubMed][CrossRef]
118. Mittrucker HW, Kohler A, Mak TW, Kaufmann SH. 1999. Critical role of CD28 in protective immunity against Salmonella typhimurium. J Immunol 163:6769–6776. [PubMed]
119. Yonekura K, Maki-Yonekura S, Namba K. 2002. Growth mechanism of the bacterial flagellar filament. Res Microbiol 153:191–197. [PubMed][CrossRef]
120. Bergman MA, Cummings LA, Alaniz RC, Mayeda L, Fellnerova I, Cookson BT. 2005. CD4+-T-cell responses generated during murine Salmonella enterica serovar Typhimurium infection are directed towards multiple epitopes within the natural antigen FliC. Infect Immun 73:7226–7235. [PubMed][CrossRef]
121. Joys TM, Schödel F. 1991. Epitope mapping of the d flagellar antigen of Salmonella muenchen. Infect Immun 59:3330–3332. [PubMed]
122. Joys TM, Street NE. 1993. Mapping of T-cell epitopes of flagellar antigen d of Salmonella muenchen. Infect Immun 61:1146–1148. [PubMed]
123. McSorley SJ, Cookson BT, Jenkins MK. 2000. Characterization of CD4+ T cell responses during natural infection with Salmonella typhimurium. J Immunol 164:986–993. [PubMed]
124. Strindelius L, Filler M, Sjoholm I. 2004. Mucosal immunization with purified flagellin from Salmonella induces systemic and mucosal immune responses in C3H/HeJ mice. Vaccine 22:3797–3808. [PubMed]
125. Gewirtz AT, Navas TA, Lyons S, Godowski PJ, Madara JL. 2001. Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J Immunol 167:1882–1885. [PubMed]
126. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A. 2001. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410:1099–1103. [PubMed][CrossRef]
127. Miao EA, Andersen-Nissen E, Warren SE, Aderem A. 2007. TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system. Semin Immunopathol 29:275–288. [PubMed][CrossRef]
128. Kutsukake K, Ohya Y, Iino T. 1990. Transcriptional analysis of the flagellar regulon of Salmonella typhimurium. J Bacteriol 172:741–747. [PubMed]
129. Cookson BT, Cummings LA, Rassoulian Barrett SL. 2001. Bacterial antigens elicit T cell responses via adaptive and transitional immune recognition. Curr. Opin. Microbiol. 4:267–273. [PubMed][CrossRef]
130. Vordermeier HM, Kotlarski I. 1990. Identification of antigens which stimulate T lymphocytes of Salmonella enteritidis 11RX immunized mice. Immunol Cell Biol 68(Pt 5):299–305. [PubMed][CrossRef]
131. Musson JA, Hayward RD, Delvig AA, Hormaeche CE, Koronakis V, Robinson JH. 2002. Processing of viable Salmonella typhimurium for presentation of a CD4 T cell epitope from the Salmonella invasion protein C (SipC). Eur J Immunol 32:2664–2671. [PubMed][CrossRef]
132. Lo WF, Woods AS, DeCloux A, Cotter RJ, Metcalf ES, Soloski MJ. 2000. Molecular mimicry mediated by MHC class Ib molecules after infection with gram-negative pathogens. Nat Med 6:215–218. [PubMed][CrossRef]
133. Ochoa-Reparaz J, Garcia B, Solano C, Lasa I, Irache JM, Gamazo C. 2005. Protective ability of subcellular extracts from Salmonella Enteritidis and from a rough isogenic mutant against salmonellosis in mice. Vaccine 23:1491–1501. [PubMed][CrossRef]
134. Ogunniyi AD, Kotlarski I, Morona R, Manning PA. 1997. Role of SefA subunit protein of SEF14 fimbriae in the pathogenesis of Salmonella enterica serovar Enteritidis. Infect Immun 65:708–717. [PubMed]
135. Ogunniyi AD, Manning PA, Kotlarski I. 1994. A Salmonella enteritidis 11RX pilin induces strong T-lymphocyte responses. Infect Immun 62:5376–5383. [PubMed]
136. Diaz-Quinonez A, Martin-Orozco N, Isibasi A, Ortiz-Navarrete V. 2004. Two Salmonella OmpC K(b)-restricted epitopes for CD8+-T-cell recognition. Infect Immun 72:3059–3062. [PubMed][CrossRef]
137. Galdiero M, De Martino L, Marcatili A, Nuzzo I, Vitiello M, Cipollaro de l’Ero G. 1998. Th1 and Th2 cell involvement in immune response to Salmonella typhimurium porins. Immunology 94:5–13. [PubMed]
138. Gupta S. 1998. Priming of T-cell responses in mice by porins of Salmonella typhimurium. Scand J Immunol 48:136–143. [PubMed][CrossRef]
139. Sood S, Rishi P, Vohra H, Sharma S, Ganguly NK. 2005. Cellular immune response induced by Salmonella enterica serotype Typhi iron-regulated outer-membrane proteins at peripheral and mucosal levels. J Med Microbiol 54:815–821. [PubMed][CrossRef]
140. Alaniz RC, Deatherage BL, Lara JC, Cookson BT. 2007. Membrane vesicles are immunogenic facsimiles of Salmonella typhimurium that potently activate dendritic cells, prime B and T cell responses, and stimulate protective immunity in vivo. J Immunol 179:7692–7701. [PubMed]
141. Kitamura D, Roes J, Kuhn R, Rajewsky K. 1991. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature 350:423–426. [PubMed][CrossRef]
142. Cunningham AF, Gaspal F, Serre K, Mohr E, Henderson IR, Scott-Tucker A, Kenny SM, Khan M, Toellner KM, Lane PJ, MacLennan IC. 2007. Salmonella induces a switched antibody response without germinal centers that impedes the extracellular spread of infection. J Immunol 178:6200–6207. [PubMed]
143. Mastroeni P, Simmons C, Fowler R, Hormaeche CE, Dougan G. 2000. Igh-6(−/−) (B-cell-deficient) mice fail to mount solid acquired resistance to oral challenge with virulent Salmonella enterica serovar typhimurium and show impaired Th1 T-cell responses to Salmonella antigens. Infect Immun 68:46–53. [PubMed][CrossRef]
144. McSorley SJ, Jenkins MK. 2000. Antibody is required for protection against virulent but not attenuated Salmonella enterica serovar typhimurium. Infect Immun 68:3344–3348. [PubMed][CrossRef]
145. Mittrucker HW, Raupach B, Kohler A, Kaufmann SH. 2000. Cutting edge: role of B lymphocytes in protective immunity against Salmonella typhimurium infection. J Immunol 164:1648–1652. [PubMed]
146. Childers NK, Bruce MG, McGhee JR. 1989. Molecular mechanisms of immunoglobulin A defense. Annu Rev Microbiol 43:503–536. [PubMed][CrossRef]
147. Michetti P, Mahan MJ, Slauch JM, Mekalanos JJ, Neutra MR. 1992. Monoclonal secretory immunoglobulin A protects mice against oral challenge with the invasive pathogen Salmonella typhimurium. Infect Immun 60:1786–1792. [PubMed]
148. Michetti P, Porta N, Mahan MJ, Slauch JM, Mekalanos JJ, Blum AL, Kraehenbuhl JP, Neutra MR. 1994. Monoclonal immunoglobulin A prevents adherence and invasion of polarized epithelial cell monolayers by Salmonella typhimurium. Gastroenterology 107:915–923. [PubMed]
149. Uren TK, Wijburg OL, Simmons C, Johansen FE, Brandtzaeg P, Strugnell RA. 2005. Vaccine-induced protection against gastrointestinal bacterial infections in the absence of secretory antibodies. Eur J Immunol 35:180–188. [PubMed][CrossRef]
150. Pecquet SS, Ehrat C, Ernst PB. 1992. Enhancement of mucosal antibody responses to Salmonella typhimurium and the microbial hapten phosphorylcholine in mice with X-linked immunodeficiency by B-cell precursors from the peritoneal cavity. Infect Immun 60:503–509. [PubMed]
151. Kantor AB, Herzenberg LA. 1993. Origin of murine B cell lineages. Annu Rev Immunol 11:501–538. [PubMed][CrossRef]
152. Whitmore AC, Haughton G, Arnold LW. 1992. Isotype switching in CD5 B cells. Ann N Y Acad Sci 651:143–151. [PubMed][CrossRef]
153. Wijburg OL, Uren TK, Simpfendorfer K, Johansen FE, Brandtzaeg P, Strugnell RA. 2006. Innate secretory antibodies protect against natural Salmonella typhimurium infection. J Exp Med 203:21–26. [PubMed][CrossRef]
154. Hormaeche CE. 1990. Dead salmonellae or their endotoxin accelerate the early course of a Salmonella infection in mice. Microb Pathog 9:213–218. [PubMed][CrossRef]
155. O’Brien AD, Metcalf ES, Rosenstreich DL. 1982. Defect in macrophage effector function confers Salmonella typhimurium susceptibility on C3H/HeJ mice. Cell Immunol 67:325–333. [PubMed][CrossRef]
156. Vidal SM, Malo D, Vogan K, Skamene E, Gros P. 1993. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73:469–485. [PubMed][CrossRef]
157. Eisenstein TK, Killar LM, Sultzer BM. 1984. Immunity to infection with Salmonella typhimurium: mouse-strain differences in vaccine- and serum-mediated protection. J Infect Dis 150:425–435. [PubMed]
158. O’Brien AD, Scher I, Metcalf ES. 1981. Genetically conferred defect in anti-Salmonella antibody formation renders CBA/N mice innately susceptible to Salmonella typhimurium infection. J Immunol 126:1368–1372. [PubMed]
159. Brown A, Hormaeche CE. 1989. The antibody response to salmonellae in mice and humans studied by immunoblots and ELISA. Microb Pathog 6:445–454. [PubMed][CrossRef]
160. Matsiota-Bernard P, Mahana W, Avrameas S, Nauciel C. 1993. Specific and natural antibody production during Salmonella typhimurium infection in genetically susceptible and resistant mice. Immunology 79:375–380. [PubMed]
161. Xu HR, Tan YY, Hsu HS, Moncure CW, Wang XM. 1993. Comparative antibody response to Salmonella antigens in genetically resistant and susceptible mice. Clin Exp Immunol 91:73–77. [PubMed]
162. Singh SP, Williams YU, Klebba PE, Macchia P, Miller S. 2000. Immune recognition of porin and lipopolysaccharide epitopes of Salmonella typhimurium in mice. Microb Pathog 28:157–167. [PubMed][CrossRef]
163. Hormaeche CE, Mastroeni P, Harrison JA, Demarco de Hormaeche R, Svenson S, Stocker BA. 1996. Protection against oral challenge three months after i.v. immunization of BALB/c mice with live Aro Salmonella typhimurium and Salmonella enteritidis vaccines is serotype (species)-dependent and only partially determined by the main LPS O antigen. Vaccine 14:251–259. [PubMed][CrossRef]
164. Lindberg AA, Segall T, Weintraub A, Stocker BA. 1993. Antibody response and protection against challenge in mice vaccinated intraperitoneally with a live aroA O4–O9 hybrid Salmonella dublin strain. Infect Immun 61:1211–1221. [PubMed]
165. Singh SP, Williams YU, Benjamin WH, Klebba PE, Boyd D. 1996. Immunoprotection by monoclonal antibodies to the porins and lipopolysaccharide of Salmonella typhimurium. Microb Pathog 21:249–263. [PubMed][CrossRef]
166. Svenson SB, Nurminen M, Lindberg AA. 1979. Artificial Salmonella vaccines: O-antigenic oligosaccharide-protein conjugates induce protection against infection with Salmonella typhimurium. Infect Immun 25:863–872. [PubMed]
167. Verdugo-Rodriguez A, Gam LH, Devi S, Koh CL, Puthucheary SD, Calva E, Pang T. 1993. Detection of antibodies against Salmonella typhi outer membrane protein (OMP) preparation in typhoid fever patients. Asian Pac J Allergy Immunol 11:45–52. [PubMed]
168. Puohiniemi R, Karvonen M, Vuopio-Varkila J, Muotiala A, Helander IM, Sarvas M. 1990. A strong antibody response to the periplasmic C-terminal domain of the OmpA protein of Escherichia coli is produced by immunization with purified OmpA or with whole E. coli or Salmonella typhimurium bacteria. Infect Immun 58:1691–1696. [PubMed]
169. Sugawara E, Nikaido H. 1994. OmpA protein of Escherichia coli outer membrane occurs in open and closed channel forms. J Biol Chem 269:17981–17987. [PubMed]
170. Singh SP, Williams YU, Miller S, Nikaido H. 2003. The C-terminal domain of Salmonella enterica serovar typhimurium OmpA is an immunodominant antigen in mice but appears to be only partially exposed on the bacterial cell surface. Infect Immun 71:3937–3946. [PubMed][CrossRef]
171. Calderon I, Lobos SR, Rojas HA, Palomino C, Rodriguez LH, Mora GC. 1986. Antibodies to porin antigens of Salmonella typhi induced during typhoid infection in humans. Infect Immun 52:209–212. [PubMed]
172. Ortiz V, Isibasi A, Garcia-Ortigoza E, Kumate J. 1989. Immunoblot detection of class-specific humoral immune response to outer membrane proteins isolated from Salmonella typhi in humans with typhoid fever. J Clin Microbiol 27:1640–1645. [PubMed]
173. De Almeida ME, Newton SM, Ferreira LC. 1999. Antibody responses against flagellin in mice orally immunized with attenuated Salmonella vaccine strains. Arch Microbiol 172:102–108. [PubMed][CrossRef]
174. Sbrogio-Almeida ME, Mosca T, Massis LM, Abrahamsohn IA, Ferreira LC. 2004. Host and bacterial factors affecting induction of immune responses to flagellin expressed by attenuated Salmonella vaccine strains. Infect Immun 72:2546–2555. [PubMed][CrossRef]
175. Tacket CO, Sztein MB, Losonsky GA, Wasserman SS, Nataro JP, Edelman R, Pickard D, Dougan G, Chatfield SN, Levine MM. 1997. Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and aroC aroD and immune response in humans. Infect Immun 65:452–456. [PubMed]
176. Humphries A, Deridder S, Baumler AJ. 2005. Salmonella enterica serotype Typhimurium fimbrial proteins serve as antigens during infection of mice. Infect Immun 73:5329–5338. [PubMed][CrossRef]
177. Levine MM, Tacket CO, Sztein MB. 2001. Host-Salmonella interaction: human trials. Microbes Infect 3:1271–1279. [PubMed]
178. Bhan MK, Bahl R, Bhatnagar S. 2005. Typhoid and paratyphoid fever. Lancet 366:749–762. [PubMed][CrossRef]
179. Arya SC, Sharma KB. 1995. Urgent need for effective vaccine against Salmonella paratyphi A, B and C. Vaccine 13:1727–1728. [PubMed][CrossRef]
180. Ochiai RL, Wang X, von Seidlein L, Yang J, Bhutta ZA, Bhattacharya SK, Agtini M, Deen JL, Wain J, Kim DR, Ali M, Acosta CJ, Jodar L, Clemens JD. 2005. Salmonella paratyphi A rates, Asia. Emerg. Infect. Dis. 11:1764–1766. [PubMed]
181. Sood S, Kapil A, Dash N, Das BK, Goel V, Seth P. 1999. Paratyphoid fever in India: an emerging problem. Emerg Infect Dis 5:483–484. [PubMed][CrossRef]
182. Vollaard AM, Ali S, Widjaja HAvan Asten S, Visser LG, Surjadi C, JTvan Dissel. 2004. Risk factors for typhoid and paratyphoid fever in Jakarta, Indonesia. JAMA 291:2607–2615. [PubMed][CrossRef]
183. Sexton K, Lennon D, Oster P, Crengle S, Martin D, Mulholland K, Percival T, Reid S, Stewart J, O’Hallahan J. 2004. The New Zealand Meningococcal Vaccine Strategy: a tailor-made vaccine to combat a devastating epidemic. N Z Med J 117:U1015. [PubMed]
184. Barr TA, Brown S, Ryan G, Zhao J, Gray D. 2007. TLR-mediated stimulation of APC: distinct cytokine responses of B cells and dendritic cells. Eur J Immunol 37:3040–3053. [PubMed][CrossRef]
185. Harris DP, Goodrich S, Mohrs K, Mohrs M, Lund FE. 2005. Cutting edge: the development of IL-4-producing B cells (B effector 2 cells) is controlled by IL-4, IL-4 receptor alpha, and Th2 cells. J Immunol 175:7103–7107. [PubMed]
186. Skok J, Poudrier J, Gray D. 1999. Dendritic cell-derived IL-12 promotes B cell induction of Th2 differentiation: a feedback regulation of Th1 development. J Immunol 163:4284–4291. [PubMed]
187. Chesnut RW, Grey HM. 1981. Studies on the capacity of B cells to serve as antigen-presenting cells. J Immunol 126:1075–1079. [PubMed]
188. Davidson HW, Watts C. 1989. Epitope-directed processing of specific antigen by B lymphocytes. J Cell Biol 109:85–92. [PubMed][CrossRef]
189. Mamula MJ, Janeway CA Jr. 1993. Do B cells drive the diversification of immune responses? Immunol. Today 14:151–154. [PubMed][CrossRef]
190. Rock KL, Benacerraf B, Abbas AK. 1984. Antigen presentation by hapten-specific B lymphocytes. I Role of surface immunoglobulin receptors J Exp Med 160:1102–1113. [PubMed][CrossRef]
191. Lanzavecchia A. 1985. Antigen-specific interaction between T and B cells. Nature 314:537–539. [PubMed][CrossRef]
192. Yrlid U, Wick MJ. 2002. Antigen presentation capacity and cytokine production by murine splenic dendritic cell subsets upon Salmonella encounter. J Immunol 169:108–116. [PubMed]
193. Garcia-del Portillo F, Stein MA, Finlay BB. 1997. Release of lipopolysaccharide from intracellular compartments containing Salmonella typhimurium to vesicles of the host epithelial cell. Infect Immun 65:24–34. [PubMed]
194. Rosenberger CM, Gallo RL, Finlay BB. 2004. Interplay between antibacterial effectors: a macrophage antimicrobial peptide impairs intracellular Salmonella replication. Proc Natl Acad Sci USA 101:2422–2427. [PubMed][CrossRef]
195. Ayabe T, Ashida T, Kohgo Y, Kono T. 2004. The role of Paneth cells and their antimicrobial peptides in innate host defense. Trends Microbiol 12:394–398. [PubMed][CrossRef]
196. Ganz T. 2003. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3:710–720. [PubMed][CrossRef]
197. Meynell GG. 1957. The applicability of the hypothesis of independent action to fatal infections in mice given Salmonella typhimurium by mouth. J Gen Microbiol 16:396–404. [PubMed]
198. Meynell GG, Stocker BA. 1957. Some hypotheses on the aetiology of fatal infections in partially resistant hosts and their application to mice challenged with Salmonella paratyphi-B or Salmonella typhimurium by intraperitoneal injection. J Gen Microbiol 16:38–58. [PubMed]
199. Gewirtz AT, Simon PO Jr, Schmitt CK, Taylor LJ, Hagedorn CH, O’Brien AD, Neish AS, Madara JL. 2001. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. J Clin Invest 107:99–109. [PubMed][CrossRef]
200. Tallant T, Deb A, Kar N, Lupica J, DiDonato MJde Veer JA. 2004. Flagellin acting via TLR5 is the major activator of key signaling pathways leading to NF-kappa B and proinflammatory gene program activation in intestinal epithelial cells. BMC Microbiol 4:33. [PubMed][CrossRef]
201. Zeng H, Carlson AQ, Guo Y, Yu Y, Collier-Hyams LS, Madara JL, Gewirtz AT, Neish AS. 2003. Flagellin is the major proinflammatory determinant of enteropathogenic Salmonella. J Immunol 171:3668–3674. [PubMed]
202. Huang FC, Werne A, Li Q, Galyov EE, Walker WA, Cherayil BJ. 2004. Cooperative interactions between flagellin and SopE2 in the epithelial interleukin-8 response to Salmonella enterica serovar typhimurium infection. Infect Immun 72:5052–5062. [PubMed][CrossRef]
203. Sierro F, Dubois B, Coste A, Kaiserlian D, Kraehenbuhl JP, Sirard JC. 2001. Flagellin stimulation of intestinal epithelial cells triggers CCL20-mediated migration of dendritic cells. Proc Natl Acad Sci USA 98:13722–13727. [PubMed][CrossRef]
204. Ramos HC, Rumbo M, Sirard JC. 2004. Bacterial flagellins: mediators of pathogenicity and host immune responses in mucosa. Trends Microbiol 12:509–517. [PubMed][CrossRef]
205. McDermott PF, Ciacci-Woolwine F, Snipes JA, Mizel SB. 2000. High-affinity interaction between gram-negative flagellin and a cell surface polypeptide results in human monocyte activation. Infect Immun 68:5525–5529. [PubMed][CrossRef]
206. Means TK, Hayashi F, Smith KD, Aderem A, Luster AD. 2003. The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells. J Immunol 170:5165–5175. [PubMed]
207. Fink SL, Cookson BT. 2005. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 73:1907–1916. [PubMed][CrossRef]
208. Hoiseth SK, Stocker BA. 1981. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature 291:238–239. [PubMed][CrossRef]
209. O’Callaghan D, Maskell D, Liew FY, Easmon CS, Dougan G. 1988. Characterization of aromatic- and purine-dependent Salmonella typhimurium: attention, persistence, and ability to induce protective immunity in BALB/c mice. Infect Immun 56:419–423. [PubMed]
210. Mastroeni P, Menager N. 2003. Development of acquired immunity to Salmonella. J Med Microbiol 52:453–459. [PubMed][CrossRef]
211. Mittrucker HW, Kaufmann SH. 2000. Immune response to infection with Salmonella typhimurium in mice. J Leukoc Biol 67:457–463. [PubMed]
212. Liao F, Rabin RL, Smith CS, Sharma G, Nutman TB, Farber JM. 1999. CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha. J Immunol 162:186–194. [PubMed]
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/content/journal/ecosalplus/10.1128/ecosalplus.8.8.11
2009-09-17
2017-05-29

Abstract:

The interaction between and its host is complex and dynamic: the host mounts an immune defense against the pathogen, which in turn acts to reduce, evade, or exploit these responses to successfully colonize the host. Although the exact mechanisms mediating protective immunity are poorly understood, it is known that T cells are a critical component of immunity to infection, and a robust T-cell response is required for both clearance of primary infection and resistance to subsequent challenge. B-cell functions, including but not limited to antibody production, are also required for generation of protective immunity. Additionally, interactions among host cells are essential. For example, antigen-presenting cells (including B cells) express cytokines that participate in CD4+ T cell activation and differentiation. Differentiated CD4+ T cells secrete cytokines that have both autocrine and paracrine functions, including recruitment and activation of phagocytes, and stimulation of B cell isotype class switching and affinity maturation. Multiple bacterium-directed mechanisms, including altered antigen expression and bioavailability and interference with antigen-presenting cell activation and function, combine to modify "pathogenic signature" in order to minimize its susceptibility to host immune surveillance. Therefore, a more complete understanding of adaptive immune responses may provide insights into pathogenic bacterial functions. Continued identification of adaptive immune targets will guide rational vaccine development, provide insights into host functions required to resist infection, and correspondingly provide valuable reagents for defining the critical pathogenic capabilities of that contribute to their success in causing acute and chronic infections.

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Figures

Image of Figure 1
Figure 1

During infection, there are several points at which pathogen and host immune cells interact. Multiple outcomes for each interaction are possible; the predominant outcome is determined not only by the virulence of the bacterium, but also the innate resistance or susceptibility of the host, and previous exposure of the host to the pathogen (host immune status). Uptake of bacteria by APCs (A) results in either APC elimination by pyroptosis (B) or APC survival (C). Pyroptosis leads to release of the inflammatory cytokines IL-1β and IL-18, and possibly releases bacteria or bacterial Ags for uptake by bystander APCs. Some APCs, such as macrophages, are capable of destroying intracellular bacteria (D). If APCs survive, they may be able to process and present Ag in the context of MHC (E). interferes with this process via multiple mechanisms including repression of Ag expression, bacterial surface modifications that reduce Ag bioavailability and APC stimulation/maturation, and other SPI-2 -dependent processes that mediate bacterial survival within the phagosome (F).

Protected from antibody detection, intracellular can utilize APCs as vehicles for systemic dissemination and replication (G). If APCs are able to overcome bacterial interference to process and present Ag to T cells (E), may still inhibit T-cell activation via stimulation of nitric oxide (NO) production and other direct, suppressive effects (H). Recognition of peptide-MHC on APCs by TCR-expressing naïve T cells leads to activation and expansion of Ag-specific effector T cells (I). Effector CD4+ T cells provide help for the activation of CD8+ CTLs (leading to cytokine production and lysis of infected host cells [J]), and B cells (K). B cells and T cells work synergistically: T cells provide help for antibody production, isotype class switching, and cytokine production by B cells, while B-cell cytokine production supports Th-1 T-cell differentiation, and Ig on B-cell surfaces mediate Ag capture for processing and presentation to T cells (K). Cytokines such as IFN-γ are produced by effector T cells to further enhance APC function and activate bacterial degradation by macrophages (L). In an immune host, previously primed Ag-specific memory T cells (M) may be activated by APCs that process and present Ag (N); activation of these cells and their effector functions (O) is much more rapid than for naïve T cells. In addition, circulating antibodies primed by previous immunization facilitate bacterial uptake via opsonization (P), accelerating the efficiency of Ag presentation up to 1,000-fold. Thus, the ultimate outcome of infection is the cumulative result of complex interactions between pathogen and host.

Citation: Cummings L, Deatherage B, Cookson B. 2009. Adaptive Immune Responses during Infection, EcoSal Plus 2009; doi:10.1128/ecosalplus.8.8.11
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Figure 2

Interactions with and its host are dynamic and complex. Flagellated and nonflagellated are present in the gut lumen (A), where they must overcome initial barriers including the glycocalyx layer, antimicrobial peptides, and sIgA. cross the epithelium (B) via M cells, by inducing endocytosis in epithelial cells, or following uptake by CX3CR1+ DCs. Bacteria in the gut lumen (A), within epithelial cells (B) and in the PP (C) express FliC protein; interaction of FliC with TLR5 initiates an inflammatory response characterized by production of IL-8 and CCL20 by epithelial cells. Release of inflammatory mediators triggers infiltration of macrophages, neutrophils, and CCR6+ DC. Interaction of these cells with results in at least three possible outcomes: (1) Phagocytosis of bacteria by DC or macrophages, ultimately resulting in inflammatory cell death (flagellin-dependent pyroptosis). Pyroptosis eliminates potential APCs, leads to release of the inflammatory cytokines IL-1β and IL-18, and possibly releases Ags for uptake by bystander APCs (note that flagellin-negative bacteria have a reduced ability to trigger inflammation via TLR5 or pyroptosis).

(2) Uptake of bacteria, which persist within the phagocyte. This interaction can lead to production of NO by APCs (inhibitory for T-cell activation) and upregulation of MHC and costimulatory molecules on DC. In addition, these cells could provide a means of transport to systemic sites such as the liver and spleen. (3) Bacteria are phagocytosed by neutrophils or macrophages and degraded. Mature CCR6+ DC in the PP (C) process and present Ags to naïve T cells; Ags acquired for processing and presentation are restricted to those expressed by bacteria in the gut lumen (A) or PP (C), or Ags that are present in gut lumen, and disassociated from the bacterial soma ([A] MVs, flagellin). Mature DCs that have processed and presented Ag on surface MHC enter into an “activation feedback” loop with naïve T cells: TNF-α and IL-12 produced by DCs enhance activation and expansion of Ag-specific T cells, while IFN-γ secretion by activated T cells further stimulates DC function. Memory T cells primed in the PP (C) express the α4β7-homing receptor as well as CCR6+, predisposing these cells to traffic to the inflamed gut during a secondary infection. Bacteria within APCs disseminate to MLN (D), where Ag presentation to T cells can also occur. Bacteria in the MLN have undergone complete adaptations to the intracellular environment: they no longer express FliC, actively reduce Ag bioavailability, and interfere with APC function (see Fig. 1 ). Dissemination to systemic sites such as liver and spleen (E) follows MLN colonization. Bacteria replicate within APCs at systemic sites. However, in naïve hosts, T-cell responses to Ags expressed by intracellular phase bacteria are generally not sufficient in magnitude or quality, or fail to develop rapidly enough, to combat infection. Further, T cells primed at early stages in the PP (C) will not recognize bacteria growing intracellularly at systemic sites (E), or that fail to express FliC in the PP (C, left).

Citation: Cummings L, Deatherage B, Cookson B. 2009. Adaptive Immune Responses during Infection, EcoSal Plus 2009; doi:10.1128/ecosalplus.8.8.11
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