1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Chronic Bacterial Pathogens: Mechanisms of Persistence

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy this Microbiology Spectrum Article
Price Non-Member $15.00
  • Authors: Mariana X. Byndloss1, Renee M. Tsolis2
  • Editors: Indira T. Kudva3, Tracy L. Nicholson4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Sacramento, CA 95817; 2: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Sacramento, CA 95817; 3: National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA; 4: National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA
  • Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0020-2015
  • Received 08 May 2015 Accepted 08 October 2015 Published 22 April 2016
  • Renee M. Tsolis, rmtsolis@ucdavis.edu
image of Chronic Bacterial Pathogens: Mechanisms of Persistence
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Chronic Bacterial Pathogens: Mechanisms of Persistence, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/4/2/VMBF-0020-2015-1.gif /docserver/preview/fulltext/microbiolspec/4/2/VMBF-0020-2015-2.gif
  • Abstract:

    Many bacterial pathogens can cause acute infections that are cleared with the onset of adaptive immunity, but a subset of these pathogens can establish persistent, and sometimes lifelong, infections. While bacteria that cause chronic infections are phylogenetically diverse, they share common features in their interactions with the host that enable a protracted period of colonization. This article will compare the persistence strategies of two chronic pathogens from the , and serovar Typhi, to consider how these two pathogens, which are very different at the genomic level, can utilize common strategies to evade immune clearance to cause chronic intracellular infections of the mononuclear phagocyte system.

  • Citation: Byndloss M, Tsolis R. 2016. Chronic Bacterial Pathogens: Mechanisms of Persistence. Microbiol Spectrum 4(2):VMBF-0020-2015. doi:10.1128/microbiolspec.VMBF-0020-2015.

References

1. Xavier MN, Winter MG, Spees AM, Nguyen K, Atluri VL, Silva TM, Baumler AJ, Muller W, Santos RL, Tsolis RM. 2013. CD4+ T cell-derived IL-10 promotes Brucella abortus persistence via modulation of macrophage function. PLoS Pathog 9:e1003454. doi:10.1371/journal.ppat.1003454. [PubMed][CrossRef]
2. Svetic A, Jian YC, Lu P, Finkelman FD, Gause WC. 1993. Brucella abortus induces a novel cytokine gene expression pattern characterized by elevated IL-10 and IFN-γ in CD4+ T cells. Int Immunol 5:877–883. [PubMed][CrossRef]
3. Atluri VL, Xavier MN, de Jong MF, den Hartigh AB, Tsolis RM. 2011. Interactions of the human pathogenic Brucella species with their hosts. Annu Rev Microbiol 65:523–541. [PubMed][CrossRef]
4. Pappas G, Papadimitriou P, Akritidis N, Christou L, Tsianos EV. 2006. The new global map of human brucellosis. Lancet Infect Dis 6:91–99. [PubMed][CrossRef]
5. Corbel MJ. 1997. Brucellosis: an overview. Emerg Infect Dis 3:213–221. [PubMed][CrossRef]
6. Crump JA, Luby SP, Mintz ED. 2004. The global burden of typhoid fever. Bull World Health Organ 82:346–353. [PubMed]
7. Keestra-Gounder AM, Tsolis RM, Baumler AJ. 2015. Now you see me, now you don’t: the interaction of Salmonella with innate immune receptors. Nat Rev Microbiol 13:206–216. [PubMed][CrossRef]
8. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R. 2012. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2095–2128. [PubMed][CrossRef]
9. House D, Bishop A, Parry C, Dougan G, Wain J. 2001. Typhoid fever: pathogenesis and disease. Curr Opin Infect Dis 14:573–578. [PubMed][CrossRef]
10. DelVecchio VG, Kapatral V, Elzer P, Patra G, Mujer CV. 2002. The genome of Brucella melitensis. Vet Microbiol 90:587–592. [PubMed][CrossRef]
11. Jennings GJ, Hajjeh RA, Girgis FY, Fadeel MA, Maksoud MA, Wasfy MO, El-Sayed N, Srikantiah P, Luby SP, Earhart K, Mahoney FJ. 2007. Brucellosis as a cause of acute febrile illness in Egypt. Trans R Soc Trop Med Hyg 101:707–713. [PubMed][CrossRef]
12. 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 IFNγ neutralization. J Exp Med 199:231–241. [PubMed][CrossRef]
13. Xavier MN, Paxão TA, den Hartigh AB, Tsolis RM, Santos RL. 2010. Pathogenesis of Brucella spp. Open Vet Sci J 4:109–118. [CrossRef]
14. Adams DO. 1976. The granulomatous inflammatory response. A review. Am J Pathol 84:164–192. [PubMed]
15. Starr T, Ng TW, Wehrly TD, Knodler LA, Celli J. 2008. Brucella intracellular replication requires trafficking through the late endosomal/lysosomal compartment. Traffic 9:678–694. [PubMed][CrossRef]
16. Anderson TD, Cheville NF. 1986. Ultrastructural morphometric analysis of Brucella abortus-infected trophoblasts in experimental placentitis. Bacterial replication occurs in rough endoplasmic reticulum. Am J Pathol 124:226–237. [PubMed]
17. Pizarro-Cerda J, Meresse S, Parton RG, van der Goot G, Sola-Landa A, Lopez-Goni I, Moreno E, Gorvel JP. 1998. Brucella abortus transits through the autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect Immun 66:5711–5724. [PubMed]
18. Celli J, de Chastellier C, Franchini DM, Pizarro-Cerda J, Moreno E, Gorvel JP. 2003. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. J Exp Med 198:545–556. [PubMed][CrossRef]
19. Rodriguez-Zapata M, Matias MJ, Prieto A, Jonde MA, Monserrat J, Sanchez L, Reyes E, De la Hera A, Alvarez-Mon M. 2010. Human brucellosis is characterized by an intense Th1 profile associated with a defective monocyte function. Infect Immun 78:3272–3279. [PubMed][CrossRef]
20. Martirosyan A, Moreno E, Gorvel J-P. 2011. An evolutionary strategy for a stealthy intracellular Brucella pathogen. Immunol Rev 240:211–234. [PubMed][CrossRef]
21. Haraga A, Ohlson MB, Miller SI. 2008. Salmonellae interplay with host cells. Nat Rev Microbiol 6:53–66. [PubMed][CrossRef]
22. Bakowski MA, Braun V, Brumell JH. 2008. Salmonella-containing vacuoles: directing traffic and nesting to grow. Traffic 9:2022–2031. [PubMed][CrossRef]
23. O’Callaghan D, Cazevieille C, Allardet-Servent A, Boschiroli ML, Bourg G, Foulongne V, Frutos P, Kulakov Y, Ramuz M. 1999. A homologue of the Agrobacterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretion systems is essential for intracellular survival of Brucella suis. Mol Microbiol 33:1210–1220. [PubMed][CrossRef]
24. Delrue RM, Martinez-Lorenzo M, Lestrate P, Danese I, Bielarz V, Mertens P, De Bolle X, Tibor A, Gorvel JP, Letesson JJ. 2001. Identification of Brucella spp. genes involved in intracellular trafficking. Cell Microbiol 3:487–497. [PubMed][CrossRef]
25. den Hartigh AB, Rolan HG, de Jong MF, Tsolis RM. 2008. VirB3-VirB6 and VirB8-VirB11, but not VirB7, are essential for mediating persistence of Brucella in the reticuloendothelial system. J Bacteriol 190:4427–4436. [PubMed][CrossRef]
26. Hong PC, Tsolis RM, Ficht TA. 2000. Identification of genes required for chronic persistence of Brucella abortus in mice. Infect Immun 68:4102–4107. [PubMed][CrossRef]
27. den Hartigh AB, Sun YH, Sondervan D, Heuvelmans N, Reinders MO, Ficht TA, Tsolis RM. 2004. Differential requirements for VirB1 and VirB2 during Brucella abortus infection. Infect Immun 72:5143–5149. [PubMed][CrossRef]
28. Zygmunt MS, Hagius SD, Walker JV, Elzer PH. 2006. Identification of Brucella melitensis 16M genes required for bacterial survival in the caprine host. Microbes Infect 8:2849–2854. [PubMed][CrossRef]
29. Roux CM, Rolan HG, Santos RL, Beremand PD, Thomas TL, Adams LG, Tsolis RM. 2007. Brucella requires a functional type IV secretion system to elicit innate immune responses in mice. Cell Microbiol 9:1851–1869. [PubMed][CrossRef]
30. Rolan HG, Tsolis RM. 2007. Mice lacking components of adaptive immunity show increased Brucella abortus virB mutant colonization. Infect Immun 75:2965–2973. [PubMed][CrossRef]
31. Rolán HG, Tsolis RM. 2008. Inactivation of the type IV secretion system reduces the Th1 polarization of the immune response to Brucella abortus infection. Infection and Immunity 76:3207–3213. [PubMed][CrossRef]
32. Gomes MT, Campos PC, Oliveira FS, Corsetti PP, Bortoluci KR, Cunha LD, Zamboni DS, Oliveira SC. 2013. Critical role of ASC inflammasomes and bacterial type IV secretion system in caspase-1 activation and host innate resistance to Brucella abortus infection. J Immunol 190:3629–3638. [PubMed][CrossRef]
33. Monack DM. 2012. Salmonella persistence and transmission strategies. Curr Opin Microbiol 15:100–107. [PubMed][CrossRef]
34. Galan JE, Curtiss R, 3rd. 1989. Cloning and molecular characterization of genes whose products allow Salmonella typhimurium to penetrate tissue culture cells. Proc Natl Acad Sci USA 86:6383–6387. [PubMed][CrossRef]
35. Khoramian-Falsafi T, Harayama S, Kutsukake K, Pechere JC. 1990. Effect of motility and chemotaxis on the invasion of Salmonella typhimurium into HeLa cells. Microb Pathog 9:47–53. [PubMed][CrossRef]
36. Libby SJ, Brehm MA, Greiner DL, Shultz LD, McClelland M, Smith KD, Cookson BT, Karlinsey JE, Kinkel TL, Porwollik S, Canals R, Cummings LA, Fang FC. 2010. Humanized nonobese diabetic-scid IL2rγnull mice are susceptible to lethal Salmonella Typhi infection. Proc Natl Acad Sci USA 107:15589–15594. [PubMed][CrossRef]
37. Hoebe K, Janssen E, Beutler B. 2004. The interface between innate and adaptive immunity. Nat Immunol 5:971–974. [PubMed][CrossRef]
38. Lapaque N, Takeuchi O, Corrales F, Akira S, Moriyon I, Howard JC, Gorvel JP. 2006. Differential inductions of TNF-alpha and IGTP, IIGP by structurally diverse classic and non-classic lipopolysaccharides. Cell Microbiol 8:401–413. [PubMed][CrossRef]
39. Conde-Alvarez R, Arce-Gorvel V, Iriarte M, Mancek-Keber M, Barquero-Calvo E, Palacios-Chaves L, Chacon-Diaz C, Chaves-Olarte E, Martirosyan A, von Bargen K, Grillo MJ, Jerala R, Brandenburg K, Llobet E, Bengoechea JA, Moreno E, Moriyon I, Gorvel JP. 2012. The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition. PLoS Pathog 8:e1002675. doi:10.1371/journal.ppat.1002675. [CrossRef]
40. Joiner KA, Puentes SM, Warren KA, Scales RA, Judd RC. 1989. Complement binding on serum-sensitive and serum-resistant transformants of Neisseria gonorrhoeae: effect of presensitization with a non-bactericidal monoclonal antibody. Microb Pathog 6:343–350. [CrossRef]
41. Barquero-Calvo E, Chaves-Olarte E, Weiss DS, Guzman-Verri C, Chacon-Diaz C, Rucavado A, Moriyon I, Moreno E. 2007. Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection. PLoS One 2:e631. doi:10.1371/journal.pone.0000631. [CrossRef]
42. Hoffmann EM, Houle JJ. 1983. Failure of Brucella abortus lipopolysaccharide (LPS) to activate the alternative pathway of complement. Vet Immunol Immunopathol 5:65–76. [PubMed][CrossRef]
43. Wilson RP, Winter SE, Spees AM, Winter MG, Nishimori JH, Sanchez JF, Nuccio SP, Crawford RW, Tukel C, Baumler AJ. 2011. The Vi capsular polysaccharide prevents complement receptor 3-mediated clearance of Salmonella enterica serotype Typhi. Infect Immun 79:830–837. [PubMed][CrossRef]
44. Zhang X, Kimura Y, Fang C, Zhou L, Sfyroera G, Lambris JD, Wetsel RA, Miwa T, Song WC. 2007. Regulation of Toll-like receptor-mediated inflammatory response by complement in vivo. Blood 110:228–236. [PubMed][CrossRef]
45. Barquero-Calvo E, Mora-Cartin R, Arce-Gorvel V, de Diego JL, Chacon-Diaz C, Chaves-Olarte E, Guzman-Verri C, Buret AG, Gorvel JP, Moreno E. 2015. Brucella abortus induces the premature death of human neutrophils through the action of its lipopolysaccharide. PLoS Pathog 11:e1004853. doi:10.1371/journal.ppat.1004853. [CrossRef]
46. Yang J, Zhao Y, Shao F. 2015. Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity. Curr Opin Immunol 32:78–83. [PubMed][CrossRef]
47. Ferooz J, Letesson JJ. 2010. Morphological analysis of the sheathed flagellum of Brucella melitensis. BMC Res Notes 3:333. [PubMed][CrossRef]
48. Fretin D, Fauconnier A, Kohler S, Halling S, Leonard S, Nijskens C, Ferooz J, Lestrate P, Delrue RM, Danese I, Vandenhaute J, Tibor A, DeBolle X, Letesson JJ. 2005. The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection. Cell Microbiol 7:687–698. [PubMed][CrossRef]
49. Andersen-Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A. 2005. Evasion of Toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci USA 102:9247–9252. [PubMed][CrossRef]
50. Terwagne M, Ferooz J, Rolan HG, Sun YH, Atluri V, Xavier MN, Franchi L, Nunez G, Legrand T, Flavell RA, De Bolle X, Letesson JJ, Tsolis RM. 2013. Innate immune recognition of flagellin limits systemic persistence of Brucella. Cell Microbiol 15:942–960. [PubMed][CrossRef]
51. Macedo GC, Magnani DM, Carvalho NB, Bruna-Romero O, Gazzinelli RT, Oliveira SC. 2008. Central role of MyD88-dependent dendritic cell maturation and proinflammatory cytokine production to control Brucella abortus infection. J Immunol 180:1080–1087. [PubMed][CrossRef]
52. Copin R, De Baetselier P, Carlier Y, Letesson JJ, Muraille E. 2007. MyD88-dependent activation of B220-CD11b+LY-6C+ dendritic cells during Brucella melitensis infection. J Immunol 178:5182–5191. [PubMed][CrossRef]
53. Salcedo SP, Marchesini MI, Lelouard H, Fugier E, Jolly G, Balor S, Muller A, Lapaque N, Demaria O, Alexopoulou L, Comerci DJ, Ugalde RA, Pierre P, Gorvel JP. 2008. Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1. PLoS Pathog 4:e21. doi:10.1371/journal.ppat.0040021. [CrossRef]
54. Cirl C, Wieser A, Yadav M, Duerr S, Schubert S, Fischer H, Stappert D, Wantia N, Rodriguez N, Wagner H, Svanborg C, Miethke T. 2008. Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. Nat Med 14:399–406. [PubMed][CrossRef]
55. Sengupta D, Koblansky A, Gaines J, Brown T, West AP, Zhang D, Nishikawa T, Park SG, Roop RM, 2nd, Ghosh S. 2010. Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL. J Immunol 184:956–964. [PubMed][CrossRef]
56. Salcedo SP, Marchesini MI, Degos C, Terwagne M, Von Bargen K, Lepidi H, Herrmann CK, Santos Lacerda TL, Imbert PR, Pierre P, Alexopoulou L, Letesson JJ, Comerci DJ, Gorvel JP. 2013. BtpB, a novel Brucella TIR-containing effector protein with immune modulatory functions. Front Cell Infect Microbiol 3:28. [PubMed][CrossRef]
57. Bignold LP, Rogers SD, Siaw TM, Bahnisch J. 1991. Inhibition of chemotaxis of neutrophil leukocytes to interleukin-8 by endotoxins of various bacteria. Infect Immun 59:4255–4258. [PubMed]
58. Wyant TL, Tanner MK, Sztein MB. 1999. Salmonella typhi flagella are potent inducers of proinflammatory cytokine secretion by human monocytes. Infect Immun 67:3619–3624. [PubMed]
59. Gewurz H, Mergenhagen SE, Nowotny A, Phillips JK. 1968. Interactions of the complement system with native and chemically modified endotoxins. J Bacteriol 95:397–405. [PubMed]
60. Baker S, Dougan G. 2007. The genome of Salmonella enterica serovar Typhi. Clin Infect Dis 45(Suppl 1):S29–S33. [PubMed][CrossRef]
61. Tischler AD, McKinney JD. 2010. Contrasting persistence strategies in Salmonella and Mycobacterium. Curr Opin Microbiol 13:93–99. [PubMed][CrossRef]
62. Arricau N, Hermant D, Waxin H, Ecobichon C, Duffey PS, Popoff MY. 1998. The RcsB-RcsC regulatory system of Salmonella typhi differentially modulates the expression of invasion proteins, flagellin and Vi antigen in response to osmolarity. Mol Microbiol 29:835–850. [PubMed][CrossRef]
63. Zhao L, Ezak T, Li ZY, Kawamura Y, Hirose K, Watanabe H. 2001. Vi-suppressed wild strain Salmonella typhi cultured in high osmolarity is hyperinvasive toward epithelial cells and destructive of Peyer’s patches. Microbiol Immunol 45:149–158. [PubMed][CrossRef]
64. Winter SE, Winter MG, Thiennimitr P, Gerriets VA, Nuccio SP, Russmann H, Baumler AJ. 2009. The TviA auxiliary protein renders the Salmonella enterica serotype Typhi RcsB regulon responsive to changes in osmolarity. Mol Microbiol 74:175–193. [PubMed][CrossRef]
65. Winter SE, Winter MG, Godinez I, Yang HJ, Russmann H, Andrews-Polymenis HL, Baumler AJ. 2010. A rapid change in virulence gene expression during the transition from the intestinal lumen into tissue promotes systemic dissemination of Salmonella. PLoS Pathog 6:e1001060. doi:10.1371/journal.ppat.1001060. [CrossRef]
66. Wangdi T, Winter SE, Baumler AJ. 2012. Typhoid fever: “you can’t hit what you can’t see”. Gut Microbes 3:88–92. [PubMed][CrossRef]
67. Winter SE, Raffatellu M, Wilson RP, Russmann H, Baumler AJ. 2008. The Salmonella enterica serotype Typhi regulator TviA reduces interleukin-8 production in intestinal epithelial cells by repressing flagellin secretion. Cell Microbiol 10:247–261. [PubMed]
68. Wangdi T, Lee CY, Spees AM, Yu C, Kingsbury DD, Winter SE, Hastey CJ, Wilson RP, Heinrich V, Baumler AJ. 2014. The Vi capsular polysaccharide enables Salmonella enterica serovar Typhi to evade microbe-guided neutrophil chemotaxis. PLoS Pathog 10:e1004306. doi:10.1371/journal.ppat.1004306. [CrossRef]
69. Kraus MD, Amatya B, Kimula Y. 1999. Histopathology of typhoid enteritis: morphologic and immunophenotypic findings. Mod Pathol 12:949–955. [PubMed]
70. Mukawi TJ. 1978. Histopathological study of typhoid perforation of the small intestines. Southeast Asian J Trop Med Public Health 9:252–255. [PubMed]
71. Tsolis RM, Young GM, Solnick JV, Baumler AJ. 2008. From bench to bedside: stealth of enteroinvasive pathogens. Nat Rev Microbiol 6:883–892. [PubMed][CrossRef]
72. Saraiva M, O’Garra A. 2010. The regulation of IL-10 production by immune cells. Nat Rev Immunol 10:170–181. [PubMed][CrossRef]
73. Couper KN, Blount DG, Riley EM. 2008. IL-10: the master regulator of immunity to infection. J Immunol 180:5771–5777. [PubMed][CrossRef]
74. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. 2001. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765. [PubMed][CrossRef]
75. Fernandes DM, Baldwin CL. 1995. Interleukin-10 downregulates protective immunity to Brucella abortus. Infect Immun 63:1130–1133. [PubMed]
76. Fernandes DM, Jiang X, Jung JH, Baldwin CL. 1996. Comparison of T cell cytokines in resistant and susceptible mice infected with virulent Brucella abortus strain 2308. FEMS Immunol Med Microbiol 16:193–203. [PubMed][CrossRef]
77. Spera JM, Ugalde JE, Mucci J, Comerci DJ, Ugalde RA. 2006. A B lymphocyte mitogen is a Brucella abortus virulence factor required for persistent infection. Proc Natl Acad Sci USA 103:16514–16519. [PubMed][CrossRef]
78. Everts B, Amiel E, van der Windt GJ, Freitas TC, Chott R, Yarasheski KE, Pearce EL, Pearce EJ. 2012. Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood 120:1422–1431. [PubMed][CrossRef]
79. West AP, Brodsky IE, Rahner C, Woo DK, Erdjument-Bromage H, Tempst P, Walsh MC, Choi Y, Shadel GS, Ghosh S. 2011. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 472:476–480. [PubMed][CrossRef]
80. O’Neill LAJ, Hardie DG. 2013. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493:346–355. [PubMed][CrossRef]
81. Rodriguez-Prados JC, Traves PG, Cuenca J, Rico D, Aragones J, Martin-Sanz P, Cascante M, Bosca L. 2010. Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J Immunol 185:605–614. [PubMed][CrossRef]
82. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, Wagner RA, Greaves DR, Murray PJ, Chawla A. 2006. Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation. Cell Metab 4:13–24. [PubMed][CrossRef]
83. Martinez FO, Sica A, Mantovani A, Locati M. 2008. Macrophage activation and polarization. Front Biosci 13:453–461. [PubMed][CrossRef]
84. Bensinger SJ, Tontonoz P. 2008. Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 454:470–477. [PubMed][CrossRef]
85. Ilhan F, Yener Z. 2008. Immunohistochemical detection of Brucella melitensis antigens in cases of naturally occurring abortions in sheep. J Vet Diagn Invest 20:803–806. [PubMed][CrossRef]
86. Magnani DM, Lyons ET, Forde TS, Shekhani MT, Adarichev VA, Splitter GA. 2013. Osteoarticular tissue infection and development of skeletal pathology in murine brucellosis. Dis Model Mech 6:811–818. [PubMed][CrossRef]
87. Xavier MN, Paixao TA, Poester FP, Lage AP, Santos RL. 2009. Pathological, immunohistochemical and bacteriological study of tissues and milk of cows and fetuses experimentally infected with Brucella abortus. J Comp Pathol 140:149–157. [PubMed][CrossRef]
88. Xavier MN, Winter MG, Spees AM, den Hartigh AB, Nguyen K, Roux CM, Silva TM, Atluri VL, Kerrinnes T, Keestra AM, Monack DM, Luciw PA, Eigenheer RA, Baumler AJ, Santos RL, Tsolis RM. 2013. PPARγ -mediated increase in glucose availability sustains chronic Brucella abortus infection in alternatively activated macrophages. Cell Host Microbe 14:159–170. [PubMed][CrossRef]
89. Meador VP, Deyoe BL, Cheville NF. 1989. Pathogenesis of Brucella abortus infection of the mammary gland and supramammary lymph node of the goat. Vet Pathol 26:357–368. [PubMed]
90. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A. 2007. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance. Nature 447:1116–1120. [PubMed][CrossRef]
91. Tontonoz P, Spiegelman BM. 2008. Fat and beyond: the diverse biology of PPARγ. Annu Rev Biochem 77:289–312. [PubMed][CrossRef]
92. Zhang L, Chawla A. 2004. Role of PPARγ in macrophage biology and atherosclerosis. Trends Endocrinol Metab 15:500–505. [PubMed][CrossRef]
93. Roop RM, 2nd, Caswell CC. 2013. Bacterial persistence: finding the “sweet spot”. Cell Host Microbe 14:119–120. [PubMed][CrossRef]
94. Eisele NA, Ruby T, Jacobson A, Manzanillo PS, Cox JS, Lam L, Mukundan L, Chawla A, Monack DM. 2013. Salmonella require the fatty acid regulator PPARδ for the establishment of a metabolic environment essential for long-term persistence. Cell Host Microbe 14:171–182. [PubMed][CrossRef]
95. Barak Y, Liao D, He W, Ong ES, Nelson MC, Olefsky JM, Boland R, Evans RM. 2002. Effects of peroxisome proliferator-activated receptor δ on placentation, adiposity, and colorectal cancer. Proc Natl Acad Sci USA 99:303–308. [PubMed][CrossRef]
microbiolspec.VMBF-0020-2015.citations
cm/4/2
content/journal/microbiolspec/10.1128/microbiolspec.VMBF-0020-2015
Loading

Citations loading...

Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.VMBF-0020-2015
2016-04-22
2017-05-26

Abstract:

Many bacterial pathogens can cause acute infections that are cleared with the onset of adaptive immunity, but a subset of these pathogens can establish persistent, and sometimes lifelong, infections. While bacteria that cause chronic infections are phylogenetically diverse, they share common features in their interactions with the host that enable a protracted period of colonization. This article will compare the persistence strategies of two chronic pathogens from the , and serovar Typhi, to consider how these two pathogens, which are very different at the genomic level, can utilize common strategies to evade immune clearance to cause chronic intracellular infections of the mononuclear phagocyte system.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Microgranuloma formation in spleen of -infected mice. Fully developed microgranuloma (black arrow) at 30 days postinfection. Granuloma is composed of epithelioid macrophages surrounded by lymphocytes. Hematoxylin and eosin stain, 400x magnification. Immunolabeling of within microgranulomas in spleen at 30 days postinfection. Note the presence of bacteria inside macrophages (black arrow). Immunohistochemistry, 400x magnification.

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0020-2015
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Macrophage metabolism during infection. During the acute phase of infection (left), interferon-γ (IFN-γ) is transiently produced, resulting in a predominance of classically activated macrophages (CAMs). In these cells, oxygen is consumed by NADPH oxidase (Phox) to generate superoxide radicals, and energy is produced by anaerobic glycolysis. Since anaerobic glycolysis yields only 2ATP, the cell has to consume more glucose to meet its energy needs. In contrast, during the chronic infection phase (right), IFN-γ is absent, but interleukin-4 (IL-4) and IL-13 signal via STAT6 to induce the alternatively activated macrophage (AAM) phenotype. Activation of STAT6 increases the expression and activation of peroxisome proliferator-activated receptor gamma (PPARγ), which in turn upregulates genes controlling β-oxidation, thereby shifting cellular physiology toward oxidative pathways. As a result, less glucose is consumed for cellular metabolism, and the intracellular glucose concentration increases. This glucose can be utilized by for growth within infected macrophages.

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0020-2015
Permissions and Reprints Request Permissions
Download as Powerpoint

Tables

Generic image for table
TABLE 1

Strategies for persistence

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0020-2015

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error