Consequences of Bacterial Invasion into Nonprofessional Phagocytic Cells

Jeffrey B. Lyczak; Gerald B. Pier

doi:10.1128/9781555818111.ch3

Chapter 3 : Consequences of Bacterial Invasion into Nonprofessional Phagocytic Cells

Authors: Jeffrey B. Lyczak¹, Gerald B. Pier¹

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Affiliations: 1: Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115

Content Type: Monograph

Publication Year: 2000

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555818111

Chapter DOI: 10.1128/9781555818111.ch3

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Abstract:

Bacterial pathogens are faced with the seemingly difficult task of persisting within their host. Bacterial invasion into host epithelium was first reported in the mid-1980s, and the study of this phenomenon has progressed in recent years to provide a more mechanistic analysis of how invasion proceeds. An overview of bacterial uptake by nonprofessional antigen-presenting cells (APCs) must consider the relevant processes with regard to both the entry and survival of the bacterial pathogen and the response of the defending host. The adaptive immune response, while able to efficiently and specifically deal with an almost infinite number of foreign antigens, is severely handicapped by the 1- to 2-week lag period required to mount a response after first exposure to a foreign substance. Apoptosis may be necessary to trigger desquamation of bacterium-laden epithelial cells. Unable to desquamate because of their nonsurface location, subsurface corneal epithelial cells support the replication of internalized bacteria, which are protected from antibody, complement, and phagocytic cells. The biochemical basis of bacterial invasion into host epithelium has been a topic of intense investigation since the late 1980s. A fuller understanding of the relative importance of these mechanisms and of the interactions that occur between them will greatly assist future strategies for prophylactic or therapeutic intervention in bacterial infectious disease.

Citation: Lyczak J, Pier G. 2000. Consequences of Bacterial Invasion into Nonprofessional Phagocytic Cells, p 41-60. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch3

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Consequences of Bacterial Invasion into Nonprofessional Phagocytic Cells

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FIGURE 1

Schematic diagram of the mucociliary clearance mechanism of the airway epithelium. The apical surface of the epithelial cells comprises many hairlike cilia, which beat in a synchronized fashion. This membrane surface is also covered with a biphasic mucous layer: the lower, or periciliary, layer is more fluid while the upper layer is more viscous. Bacteria get trapped in the viscous layer and are carried upward due to the ciliary beating and are eventually expectorated and swallowed.

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FIGURE 1

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FIGURE 2

A summary of epithelial cell receptors, which mediate adhesion and invasion of bacteria into epithelial cells. The bacterium shown is a generic diagram and contains elements of both gram-positive and gram-negative bacteria. LPS, lipopolysaccharide.

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FIGURE 2

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FIGURE 3

Mechanisms by which epithelial cells recruit and activate immune effector cells following epithelial cell infection. (A) Infected epithelial cells secrete proinflammatory cytokines such as IL-1β and TNF-α (which are chemotactic for a number of immune effector cells). (B) Infected epithelial cells begin to express class II MHC proteins on their surface, allowing them to function as “nonprofessional” APCs for helper T lymphocytes. (C) Infected epithelial cells undergo apoptosis. Apoptotic bodies released from dead cells are subsequently phagocytosed by dendritic cells, which then present antigens to T lymphocytes.

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FIGURE 3

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FIGURE 4

Expression of class II MHC by epithelial cells following internalization of bacteria. Step 1: synthesis of class II MHC can be induced by bacterial internalization through the apical plasma membrane or by exposure to a milieu of proinflammatory cytokines. Step 2: class II MHC is synthesized and intersects endocytic vacuoles containing endocytosed antigen. Step 3: vesicles containing complexes of bacterial antigens and nascent MHC protein are trafficked exclusively to the basolateral membrane of the epithelial cell, thus ensuring antigen presentation to T lymphocytes in the underlying submucosal tissue.

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FIGURE 4

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FIGURE 5

Diapedesis of neutrophils (shown in gray) disrupts tight junctions between epithelial cells (shown in white). The resulting disruption may provide an access point for bacteria (shown in black), allowing them to cross the epithelium and reach deeper tissues.

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FIGURE 5

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FIGURE 6

Invasion of bacteria into nonprofessional phagocytes allows bacterial proliferation and spread. Diagram A depicts the intracellular replication of bacteria within host epithelium, as has been demonstrated to occur in the case of several microorganisms including P. aeruginosa and serovar Typhi. Diagram B illustrates that invasion of bacteria into a nonprofessional phagocytic host can serve as a means of accessing deeper host tissues. The specific example shown in the figure depicts serovar Typhi passing through the intestinal epithelium to reach a host macrophage, which it then infects and uses to disseminate throughout the host's body.

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FIGURE 6

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FIGURE 7

Two models intended to explain the differential outcome of CFTRmediated internalization of P. aeruginosa in two different host tissues. (A) In the airway, internalization of P. aeruginosa induces apoptosis of bacterium-laden epithelial cells. These epithelial cells detach from the tissue and are expectorated, thus removing the bacteria they contain from the airways. It is possible that apoptotic bodies derived from the bacterium-laden cells are phagocytosed by dendritic cells and presented to helper T cells by the dendritic cell. (B) In the cornea, bacteria that breach the superficial, squamous epithelial cells are internalized by basal epithelial cells. Due to their anatomic location, the bacterium-laden epithelial cells are unable to desquamate and serve instead as a niche for the replication of intracellular bacteria.

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FIGURE 7

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FIGURE 8

Actin motility (also called “rocket motility”) of S. flexneri after its invasion of a host epithelial cell. (A) After invasion of the epithelial cell, Shigella escapes the endocytic vacuole and then forms actin filaments that propel the Shigella from its original host epithelial cell to adjacent cells. (B) Formation of actin filaments requires the participation of bacterial proteins such as IcsA, as well as the recruitment of host cytoskeletal elements vinculin and actin. Synthesis of IcsA is asymmetric on the bacterial cell, resulting in the formation of actin filaments on only one pole of the bacterium (the “old” pole). Vinculin binds IcsA, initiating the polymerization of actin.

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FIGURE 8

References

/content/book/10.1128/9781555818111.chap3

1. Agerberth, B.,, J. Grunewald,, E. Castanos- Velez,, B. Olsson,, H. Jornvall,, H. Wigzell,, A. Eklund,, and G. H. Gudmundsson. 1999. Antibacterial components in bronchoalveolar lavage fluid from healthy individuals and sarcoidosis patients. Am. J. Respir. Crit. Care Med. 160: 283– 290.

2. Beck-Schimmer, B.,, R. C. Schimmer,, R. L. Warner,, H. Schmal,, G. Nordblom, et al. 1997. Expression of lung vascular and airway ICAM-1 after exposure to bacterial lipopolysaccharide. Am. J. Respir. Cell Mol. Biol. 17: 344– 352.

3. Brandtzaeg, P.,, T. S. Halstensen,, H. S. Huitfeldt,, P. Krajci,, D. Kvale,, H. Scott,, and P. S. Thrane. 1992. Epithelial expression of HLA, secretory component (poly-Ig receptor), and adhesion molecules in the human alimentary tract. Ann. N.Y. Acad. Sci. 664: 157– 179.

4. Brogden, K. A.,, M. R. Ackermann,, P. B. McCray, Jr.,, and K. M. Huttner. 1999. Differences in the concentrations of small, anionic, antimicrobial peptides in bronchoalveolar lavage fluid and in respiratory epithelia of patients with and without cystic fibrosis. Infect. Immun. 67: 4256– 4259.

5. Bryan, R.,, D. Kube,, A. Perez,, P. Davis,, and A. Prince. 1998. Overproduction of the CFTR R domain leads to increased levels of asialoGM1 and increased Pseudomonas aeruginosa binding by epithelial cells. Am. J. Respir. Cell Mol. Biol. 19: 269– 277.

6. Buommino, E.,, F. Morelli,, S. Metafora,, F. Rossano,, B. Perfetto,, A. Baroni,, and M. A. Tufano. 1999. Porin from Pseudomonas aeruginosa induces apoptosis in an epithelial cell line derived from rat seminal vesicles. Infect. Immun. 67: 4794– 4800.

7. Burns, J. L.,, M. Jonas,, E. Y. Chi,, D. K. Clark,, A. Berger,, and A. Griffith. 1996 Invasion of respiratory epithelial cells by Burkholderia ( Pseudomonas) cepacia. Infect. Immun. 64: 4054– 4059.

8. Christensen, P. J.,, S. Kim,, R. H. Simon,, G. B. Toews,, and R. D. Paine. 1993. Differentiation- related expression of ICAM-1 by rat alveolar epithelial cells. Am. J. Respir. Cell Mol. Biol. 8: 9– 15.

9. Clark, D. A.,, P. J. Lamey,, R. F. Jarrett,, and D. E. Onions. 1994. A model to study viral and cytokine involvement in Sjogren’s syndrome. Autoimmunity 18: 7– 14.

10. Comolli, J. C.,, L. L. Waite,, K. E. Mostov,, and J. N. Engel. 1999. Pili binding to asialo- GM1 on epithelial cells can mediate cytotoxicity or bacterial internalization by Pseudomonas aeruginosa. Infect. Immun. 67: 3207– 3214.

11. Conte, M. P.,, G. Petrone,, C. Longhi,, P. Valenti,, R. Morelli,, F. Superti,, and L. Seganti 1996. The effects of inhibitors of vacuolar acidification on the release of Listeria monocytogenes from phagosomes of Caco-2 cells. J. Med. Microbiol. 44: 418– 424.

12. d’Hauteville, H.,, and P. J. Sansonetti. 1992. Phosphorylation of IcsA by cAMP-dependent protein kinase and its effect on intracellular spread of Shigella flexneri. Mol. Microbiol. 6: 833– 841.

13. Daisy, J. A.,, C. E. Benson,, J. McKitrick,, and H. M. Friedman. 1981. Intracellular replication of Legionella pneumophila. J. Infect. Dis. 143: 460– 464.

14. Dang, L. H.,, M. T. Michalek,, F. Takei,, B. Benaceraff,, and K. L. Rock. 1990. Role of ICAM-1 in antigen presentation demonstrated by ICAM-1 defective mutants. J. Immunol. 144: 4082– 4091.

15. de Bentzmann, S.,, P. Roger,, and E. Puchelle. 1996. Pseudomonas aeruginosa adherence to remodelling respiratory epithelium. Eur. Respir. J. 9: 2145– 2150.

16. De Panfilis, G.,, G. C. Manara,, C. Ferrari,, C. Torresani,, and A. Lonati. 1992. Adhesion molecules on the plasma membrane of epidermal cells. IV. Immunolocalization of the intercellular adhesion molecule-1 (ICAM-1, CD54) on the cell surface of a small subpopulation of keratinocytes freshly isolated from normal human epidermis. Reg. Immunol. 4: 119– 129.

17. Dehio, C.,, M. C. Prevost,, and P. J. Sansonetti. 1995. Invasion of epithelial cells by Shigella flexneri induces tyrosine phosphorylation of cortactin by a pp60c-src-mediated signalling pathway. EMBO J. 14: 2471– 2482.

18. Denning, S. M.,, D. T. Tuck,, L. W. Vollger,, T. A. Springer,, K. H. Singer,, and B. F. Haynes. 1987. Monoclonal antibodies to CD2 and lymphocyte function-associated antigen 3 inhibit human thymic epithelial cell-dependent mature thymocyte activation. J. Immunol. 139: 2573– 2578.

19. Eckle, I.,, G. Kolb,, and K. Havemann. 1991. Inhibition of neutrophil chemotaxis by elastasegenerated IgG fragments. Scand. J. Immunol. 34: 359– 364.

20. Eckmann, L.,, H. C. Jung,, C. Schurer-Maly,, A. Panja,, E. Morzycka-Wroblewska,, and M. F. Kagnoff. 1993. Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin 8 [comment]. Gastroenterology 105: 1689– 1697.

21. Elner, S. G.,, R. M. Strieter,, V. M. Elner,, B. J. Rollins,, M. A. Del Monte,, and S. L. Kunkel. 1991. Monocyte chemotactic protein gene expression by cytokine-treated human retinal pigment epithelial cells. Lab. Invest. 64: 819– 825.

22. Elner, V. M.,, R. M. Strieter,, S. G. Elner,, M. Baggiolini,, I. Lindley,, and S. L. Kunkel. 1990. Neutrophil chemotactic factor (IL-8) gene expression by cytokine-treated retinal pigment epithelial cells. Am. J. Pathol. 136: 745– 750.

23. Eriksson, K.,, E. Ahlfors,, A. George- Chandy,, D. Kaiserlian,, and C. Czerkinsky. 1996. Antigen presentation in the murine oral epithelium. Immunology 88: 147– 152.

24. Feldman, M.,, R. Bryan,, S. Rajan,, L. Scheffler,, S. Brunnert,, H. Tang,, and A. Prince. 1998. Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection. Infect. Immun. 66: 43– 51.

25. Finlay, B. B.,, J. Fry,, E. P. Rock,, and S. Falkow. 1989. Passage of Salmonella through polarized epithelial cells: role of the host and bacterium. J. Cell Sci. Suppl. 11: 99– 107.

26. Finlay, B. B.,, F. Heffron,, and S. Falkow. 1989. Epithelial cell surfaces induce Salmonella proteins required for bacterial adherence and invasion. Science 243: 940– 943.

27. Fleiszig, S. M.,, T. S. Zaidi,, and G. B. Pier. 1995. Pseudomonas aeruginosa invasion of and multiplication within corneal epithelial cells in vitro. Infect. Immun. 63: 4072– 4077.

28. Franzetti, F.,, M. Cernuschi,, R. Esposito,, and M. Moroni. 1992. Pseudomonas infections in patients with AIDS and AIDS-related complex. J. Intern. Med. 231: 437– 443.

29. Fujiwara, Y.,, T. Arakawa,, T. Fukuda,, E. Sasaki,, K. Nakagawa,, K. Fujiwara,, K. Higuchi,, K. Kobayashi,, and A. Tarnawski. 1997. Interleukin-8 stimulates leukocyte migration across a monolayer of cultured rabbit gastric epithelial cells. Effect associated with the impairment of gastric epithelial barrier function. Dig. Dis. Sci. 42: 1210– 1215.

30. Gaillard, J. L.,, P. Berche,, J. Mounier,, S. Richard,, and P. Sansonetti. 1987. In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocytelike cell line Caco-2. Infect. Immun. 55: 2822– 2829.

31. Galan, J. E.,, and R. D. Curtiss. 1990. Expression of Salmonella typhimurium genes required for invasion is regulated by changes in DNA supercoiling. Infect. Immun. 58: 1879– 1885.

32. Galan, J. E.,, C. Ginocchio,, and P. Costeas. 1992. Molecular and functional characterization of the Salmonella invasion gene invA: homology of InvA to members of a new protein family. J. Bacteriol. 174: 4338– 4349.

33. Goldfine, H.,, C. Knob,, D. Alford,, and J. Bentz. 1995. Membrane permeabilization by Listeria monocytogenes phosphatidylinositolspecific phospholipase C is independent of phospholipid hydrolysis and cooperative with listeriolysin O. Proc. Natl. Acad. Sci. USA 92: 2979– 2983. (Retraction, Proc. Natl. Acad. Sci. USA, 1997, 94:2772.)

34. Goldman, M. J.,, G. M. Anderson,, E. D. Stolzenberg,, U. P. Kari,, M. Zasloff,, and J. M. Wilson. 1997. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88: 553– 560.

35. Govan, J. R.,, and V. Deretic. 1996. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol. Rev. 60: 539– 574.

36. Govan, J. R.,, and J. W. Nelson. 1992. Microbiology of lung infection in cystic fibrosis. Br. Med. Bull. 48: 912– 930.

37. Greenfield, E. A.,, K. A. Nguyen,, and V. K. Kuchroo. 1998. CD28/B7 costimulation: a review. Crit. Rev. Immunol. 18: 389– 418.

38. Gupta, S. K.,, R. S. Berk,, S. Masinick,, and L. D. Hazlett. 1994. Pili and lipopolysaccharide of Pseudomonas aeruginosa bind to the glycolipid asialo GM1. Infect. Immun. 62: 4572– 4579.

39. Hale, T. L. 1986. Invasion of epithelial cells by shigellae. Ann. Inst. Pasteur Microbiol. 137A: 311– 314.

40. Hauser, A. R.,, and J. N. Engel. 1999. Pseudomonas aeruginosa induces type-III-secretionmediated apoptosis of macrophages and epithelial cells. Infect. Immun. 67: 5530– 5537.

41. Hershberg, R. M.,, D. H. Cho,, A. Youakim,, M. B. Bradley,, J. S. Lee,, P. E. Framson,, and G. T. Nepom. 1998. Highly polarized HLA class II antigen processing and presentation by human intestinal epithelial cells. J. Clin. Invest. 102: 792– 803.

42. High, N.,, J. Mounier,, M. C. Prevost,, and P. J. Sansonetti. 1992. IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J. 11: 1991– 1999.

43. Housseau, F.,, N. Rouas-Freiss,, M. Roy,, J. M. Bidart,, J. G. Guillet,, and D. Bellet. 1997. Antigen-presenting function of murine gonadal epithelial cell lines. Cell. Immunol. 177: 93– 101.

44. Htin, A. 1990. T lymphocyte motility toward IL-1 in patients with interstitial lung diseases. Bull. Chest Dis. Res. Inst. Kyoto Univ. 23: 38– 47.

45. Imai, Y.,, M. Yamakawa,, and T. Kasajima. 1998. The lymphocyte-dendritic cell system. Histol. Histopathol. 13: 469– 510..

46. Ivanoff, B.,, M. M. Levine,, and P. H. Lambert. 1994. Vaccination against typhoid fever: present status. Bull. W. H. O. 72: 957– 971.

47. Jones, B. D.,, N. Ghori,, and S. Falkow. 1994. Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer’s patches [see comments]. J. Exp. Med. 180: 15– 23.

48. Jones, N. L.,, A. S. Day,, H. A. Jennings,, and P. M. Sherman. 1999. Helicobacter pylori induces gastric epithelial cell apoptosis in association with increased Fas receptor expression. Infect. Immun. 67: 4237– 4242.

49. Jorens, P. G.,, J. B. Richman-Eisenstat,, B. P. Housset,, P. P. Massion,, I. Ueki,, and J. A. Nadel. 1994. Pseudomonas-induced neutrophil recruitment in the dog airway in vivo is mediated in part by IL-8 and inhibited by a leumedin. Eur. Respir. J. 7: 1925– 1931.

50. Kaiserlian, D.,, D. Rigal,, J. Abello,, and J. P. Revillard. 1991. Expression, function and regulation of the intercellular adhesion molecule-1 (ICAM-1) on human intestinal epithelial cell lines. Eur. J. Immunol. 21: 2415– 2421.

51. Kharazmi, A.,, H. Nielsen,, and K. Bendtzen. 1988. Modulation of human neutrophil and monocyte chemotaxis and superoxide responses by recombinant TNF-alpha and GM-CSF. Immunobiology 177: 363– 370.

52. Kielhofner, M.,, R. L. Atmar,, R. J. Hamill,, and D. M. Musher. 1992. Life-threatening Pseudomonas aeruginosa infections in patients with human immunodeficiency virus infection. Clin. Infect. Dis. 14: 403– 411.

53. Kim, J. M.,, L. Eckmann,, T. C. Savidge,, D. C. Lowe,, T. Witthoft,, and M. F. Kagnoff. 1998. Apoptosis of human intestinal epithelial cells after bacterial invasion. J. Clin. Invest. 102: 1815– 1823.

54. Konturek, P. C.,, P. Pierzchalski,, S. J. Konturek,, H. Meixner,, G. Faller,, T. Kirchner,, and E. G. Hahn. 1999. Helicobacter pylori induces apoptosis in gastric mucosa through an upregulation of Bax expression in humans. Scand. J. Gastroenterol. 34: 375– 383.

55. Krivan, H. C.,, D. D. Roberts,, and V. Ginsburg. 1988. Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAc beta 1-4Gal found in some glycolipids. Proc. Natl. Acad. Sci. USA 85: 6157– 6161.

56. Kunkel, S. L.,, T. Standiford,, K. Kasahara,, and R. M. Strieter. 1991. Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp. Lung Res. 17: 17– 23.

57. Laine, R. O.,, W. Zeile,, F. Kang,, D. L. Purich,, and F. S. Southwick. 1997. Vinculin proteolysis unmasks an ActA homolog for actin-based Shigella motility. J. Cell Biol. 138: 1255– 1264.

58. Lam, J.,, R. Chan,, K. Lam,, and J. W. Costerton. 1980. Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis. Infect. Immun. 28: 546– 556.

59. Lee, K. K.,, H. B. Sheth,, W. Y. Wong,, R. Sherburne,, W. Paranchych,, R. S. Hodges,, C. A. Lingwood,, H. Krivan,, and R. T. Irvin. 1994. The binding of Pseudomonas aeruginosa pili to glycosphingolipids is a tip-associated event involving the C-terminal region of the structural pilin subunit. Mol. Microbiol. 11: 705– 713.

60. Leung, K. Y.,, and B. B. Finlay. 1991. Intracellular replication is essential for the virulence of Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 88: 11470– 11474.

61. Li, X. C.,, A. M. Jevnikar,, and D. R. Grant. 1997. Expression of functional ICAM-1 and VCAM-1 adhesion molecules by an immortalized epithelial cell clone derived from the small intestine. Cell Immunol. 175: 58– 66.

62. Maekawa, T.,, Y. Kinoshita,, Y. Matsushima,, A. Okada,, H. Fukui, et al. 1997. Helicobacter pylori induces proinflammatory cytokines and major histocompatibility complex class II antigen in mouse gastric epithelial cells. J. Lab. Clin. Med. 130: 442– 449.

63. Medzhitov, R.,, and C. A. Janeway, Jr. 1998. Innate immune recognition and control of adaptive immune responses. Semin. Immunol. 10: 351– 353.

64. Mellman, I.,, S. J. Turley,, and R. M. Steinman. 1998. Antigen processing for amateurs and professionals. Trends Cell Biol. 8: 231– 237.

65. Meyer, K. C.,, and J. Zimmerman. 1993. Neutrophil mediators, Pseudomonas, and pulmonary dysfunction in cystic fibrosis [see comments]. J. Lab. Clin. Med. 121: 654– 661.

66. Miller, V. L.,, and S. Falkow. 1988. Evidence for two genetic loci in Yersinia enterocolitica that can promote invasion of epithelial cells. Infect. Immun. 56: 1242– 1248.

67. Mounier, J.,, A. Ryter,, M. Coquis-Rondon,, and P. J. Sansonetti. 1990. Intracellular and cell-to-cell spread of Listeria monocytogenes involves interaction with F-actin in the enterocytelike cell line Caco-2. Infect. Immun. 58: 1048– 1058.

68. Mulvey, M. A.,, Y. S. Lopez-Boado,, C. L. Wilson,, R. Roth,, W. C. Parks,, J. Heuser,, and S. J. Hultgren. 1998. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282: 1494– 1497. [ Erratum, Science, 1999, 283:795.]

69. Nadel, J. A.,, B. Davis,, and R. J. Phipps. 1979. Control of mucus secretion and ion transport in airways. Annu. Rev. Physiol. 41: 369– 381.

70. Nagineni, C. N.,, R. K. Kutty,, B. Detrick,, and J. J. Hooks. 1996. Inflammatory cytokines induce intercellular adhesion molecule-1 (ICAM- 1) mRNA synthesis and protein secretion by human retinal pigment epithelial cell cultures. Cytokine 8: 622– 630.

71. Nakagawa, H.,, K. Watanabe,, and K. Sato. 1988. Inhibitory action of synthetic proteinase inhibitors and substrates on the chemotaxis of rat polymorphonuclear leukocytes in vitro. J. Pharmacobiodyn. 11: 674– 678.

72. Nash, S.,, J. Stafford,, and J. L. Madara. 1987. Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers. J. Clin. Invest. 80: 1104– 1113.

73. Newell, D. G.,, and A. Pearson. 1984. The invasion of epithelial cell lines and the intestinal epithelium of infant mice by Campylobacter jejuni/coli. J. Diarrhoeal Dis. Res. 2: 19– 26.

74. Niesel, D. W.,, C. B. Hess,, Y. J. Cho,, K. D. Klimpel,, and G. R. Klimpel. 1986. Natural and recombinant interferons inhibit epithelial cell invasion by Shigella spp. Infect. Immun. 52: 828– 833.

75. Oldham, L. J.,, and F. G. Rodgers. 1985. Adhesion, penetration and intracellular replication of Legionella pneumophila: an in vitro model of pathogenesis. J. Gen. Microbiol. 131: 697– 706.

76. Osusky, R.,, R. J. Dorio,, Y. K. Arora,, S. J. Ryan,, and S. M. Walker. 1997. MHC class II positive retinal pigment epithelial (RPE) cells can function as antigen-presenting cells for microbial superantigen. Ocul. Immunol. Inflamm. 5: 43– 50.

77. Pace, J.,, M. J. Hayman,, and J. E. Galan. 1993. Signal transduction and invasion of epithelial cells by S. typhimurium. Cell 72: 505– 514.

78. Pace, J. L.,, and J. E. Galan. 1994. Measurement of free intracellular calcium levels in epithelial cells as consequence of bacterial invasion. Methods Enzymol. 236: 482– 490.

79. Panjwani, N.,, T. S. Zaidi,, J. E. Gigstad,, F. B. Jungalwala,, M. Barza,, and J. Baum. 1990. Binding of Pseudomonas aeruginosa to neutral glycosphingolipids of rabbit corneal epithelium. Infect. Immun. 58: 114– 118.

80. Patel, J. A.,, M. Kunimoto,, T. C. Sim,, R. Garofalo,, T. Eliott, et al. 1995. Interleukin-1 alpha mediates the enhanced expression of intercellular adhesion molecule-1 in pulmonary epithelial cells infected with respiratory syncytial virus. Am. J. Respir. Cell Mol. Biol. 13: 602– 609.

81. Perdomo, J. J.,, P. Gounon,, and P. J. Sansonetti. 1994. Polymorphonuclear leukocyte transmigration promotes invasion of colonic epithelial monolayer by Shigella flexneri. J. Clin. Invest. 93: 633– 643.

82. Pier, G. B.,, M. Grout,, T. Zaidi,, G. Meluleni,, S. S. Mueschenborn,, G. Banting,, R. Ratcliff,, M. J. Evans,, and W. H. Colledge. 1998. Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature 393: 79– 82.

83. Pier, G. B.,, M. Grout,, and T. S. Zaidi. 1997. Cystic fibrosis transmembrane conductance regulator is an epithelial cell receptor for clearance of Pseudomonas aeruginosa from the lung. Proc. Natl. Acad. Sci. USA 94: 12088– 12093.

84. Pier, G. B.,, M. Grout,, T. S. Zaidi,, and J. B. Goldberg. 1996. How mutant CFTR may contribute to Pseudomonas aeruginosa infection in cystic fibrosis. Am. J. Respir. Crit. Care Med. 154: S175– S182.

85. Pier, G. B.,, M. Grout,, T. S. Zaidi,, J. C. Olsen,, L. G. Johnson,, J. R. Yankaskas,, and J. B. Goldberg. 1996. Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections. Science 271: 64– 67.

86. Rosenshine, I.,, S. Ruschkowski,, V. Foubister,, and B. B. Finlay. 1994. Salmonella typhimurium invasion of epithelial cells: role of induced host cell tyrosine protein phosphorylation. Infect. Immun. 62: 4969– 4974.

87. Rovere, P.,, A. A. Manfredi,, C. Vallinoto,, V. S. Zimmermann,, U. Fascio, et al. 1998. Dendritic cells preferentially internalize apoptotic cells opsonized by anti-beta2-glycoprotein I antibodies. J. Autoimmun. 11: 403– 411.

88. Rovere, P.,, C. Vallinoto,, A. Bondanza,, M. C. Crosti,, M. Rescigno,, P. Ricciardi- Castagnoli,, C. Rugarli,, and A. A. Manfredi. 1998. Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function. J. Immunol. 161: 4467– 4471.

89. Rubens, C. E.,, S. Smith,, M. Hulse,, E. Y. Chi,, and G. van Belle. 1992. Respiratory epithelial cell invasion by group B streptococci. Infect. Immun. 60: 5157– 5163.

90. Saiman, L.,, and A. Prince. 1993. Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells. J. Clin. Invest. 92: 1875– 1880.

91. Sandros, J.,, P. N. Madianos,, and P. N. Papapanou. 1996. Cellular events concurrent with Porphyromonas gingivalis invasion of oral epithelium in vitro. Eur. J. Oral Sci. 104: 363– 371.

92. Sansonetti, P. J. 1991. Genetic and molecular basis of epithelial cell invasion by Shigella species. Rev. Infect. Dis. 13( Suppl 4): S285– S292.

93. Sansonetti, P. J.,, A. Ryter,, P. Clerc,, A. T. Maurelli,, and J. Mounier. 1986. Multiplication of Shigella flexneri within HeLa cells: lysis of the phagocytic vacuole and plasmid-mediated contact hemolysis. Infect. Immun. 51: 461– 469.

94. Sayers, T. J.,, T. A. Wiltrout,, C. A. Bull,, A. C. Denn,, A. M. Pilaro,, and B. Lokesh. 1988. Effect of cytokines on polymorphonuclear neutrophil infiltration in the mouse. Prostaglandin- and leukotriene-independent induction of infiltration by IL-1 and tumor necrosis factor. J. Immunol. 141: 1670– 1677.

95. Schnapp, D.,, and A. Harris. 1998. Antibacterial peptides in bronchoalveolar lavage fluid. Am. J. Respir. Cell Mol. Biol. 19: 352– 356.

96. Schurr, M. J.,, D. W. Martin,, M. H. Mudd,, N. S. Hibler,, J. C. Boucher,, and V. Deretic. 1993. The algD promoter: regulation of alginate production by Pseudomonas aeruginosa in cystic fibrosis. Cell Mol. Biol. Res. 39: 371– 376.

97. Shere, K. D.,, S. Sallustio,, A. Manessis,, T. G. D’Aversa,, and M. B. Goldberg. 1997. Disruption of IcsP, the major Shigella protease that cleaves IcsA, accelerates actin-based motility. Mol. Microbiol. 25: 451– 462.

98. Shimizu, A.,, A. Takeuchi,, H. Ohto,, T. Hashimoto,, and T. Miyamoto. 1988. Inhibition of neutrophil chemotaxis by a monoclonal antibody (TM316). Scand. J. Immunol. 28: 675– 685.

99. Shimizu, T.,, C. X. Cao,, R. G. Shao,, and Y. Pommier. 1998. Lamin B phosphorylation by protein kinase calpha and proteolysis during apoptosis in human leukemia HL60 cells. J. Biol. Chem. 273: 8669– 8674.

100. Siu, G.,, S. M. Hedrick,, and A. A. Brian. 1989. Isolation of the murine intercellular adhesion molecule 1 (ICAM-1) gene. ICAM-1 enhances antigen-specific T cell activation. J. Immunol. 143: 3813– 3820.

101. Smart, S. J.,, and T. B. Casale. 1994. Pulmonary epithelial cells facilitate TNF-alphainduced neutrophil chemotaxis. A role for cytokine networking. J. Immunol. 152: 4087– 4094.

102. Smith, J. J.,, S. M. Travis,, E. P. Greenberg,, and M. J. Welsh. 1996. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 85: 229– 236. [ Erratum, Cell, 1996, 87:following 355.]

103. Standiford, T. J.,, S. L. Kunkel,, M. A. Basha,, S. W. Chensue,, J. P. Lynch,, G. B. Toews,, J. Westwick,, and R. M. Strieter. 1990. Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. J. Clin. Invest. 86: 1945– 1953.

104. Stein, M. E.,, and M. J. Stadecker. 1987. Characterization and antigen-presenting function of a murine thyroid-derived epithelial cell line. J. Immunol. 139: 1786– 1791.

105. Steinhauer, J.,, R. Agha,, T. Pham,, A. W. Varga,, and M. B. Goldberg. 1999. The unipolar Shigella surface protein IcsA is targeted directly to the bacterial old pole: IcsP cleavage of IcsA occurs over the entire bacterial surface. Mol. Microbiol. 32: 367– 377.

106. Suzuki, T.,, S. Saga,, and C. Sasakawa. 1996. Functional analysis of Shigella VirG domains essential for interaction with vinculin and actin-based motility. J. Biol. Chem. 271: 21878– 21885.

107. Svanborg, C.,, W. Agace,, S. Hedges,, H. Linder,, and M. Svensson. 1993. Bacterial adherence and epithelial cell cytokine production. Zentralbl. Bakteriol. 278: 359– 364.

108. Takahashi, I.,, and H. Kiyono. 1999. Gut as the largest immunologic tissue. J. Parenter. Enteral Nutr., in press.

109. Takaya, M.,, Y. Ichikawa,, H. Shimizu,, M. Uchiyama,, J. Moriuchi,, and S. Arimori. 1990. Expression of MHC class II antigens and other T cell activation antigens on T cells and salivary duct epithelial cells in the salivary gland of cases of Sjogren’s syndrome. Tokai J. Exp. Clin. Med. 15: 27– 33.

110. Taylor, J. L.,, and W. J. O’Brien. 1985. Interferon production and sensitivity of rabbit corneal epithelial and stromal cells. Invest. Ophthalmol. Vis. Sci. 26: 1502– 1508.

111. Tosi, M. F.,, J. M. Stark,, C. W. Smith,, A. Hamedani,, D. C. Gruenert,, and M. D. Infeld. 1992. Induction of ICAM-1 expression on human airway epithelial cells by inflammatory cytokines: effects on neutrophil-epithelial cell adhesion. Am. J. Respir. Cell Mol. Biol. 7: 214– 221.

112. Tuteja, R.,, and N. Tuteja. 1998. Nucleolin: a multifunctional major nucleolar phosphoprotein. Crit. Rev. Biochem. Mol. Biol. 33: 407– 436.

113. Vejlsgaard, G. L.,, E. Ralfkiaer,, C. Avnstorp,, M. Czajkowski,, S. D. Marlin,, and R. Rothlein. 1989. Kinetics and characterization of intercellular adhesion molecule-1 (ICAM-1) expression on keratinocytes in various inflammatory skin lesions and malignant cutaneous lymphomas. J. Am. Acad. Dermatol. 20: 782– 790.

114. Webster, P.,, L. Vanacore,, A. C. Nairn,, and C. R. Marino. 1994. Subcellular localization of CFTR to endosomes in a ductal epithelium. Am. J. Physiol. 267: C340– C348.

115. Yard, B. A.,, M. R. Daha,, M. Kooymans- Couthino,, J. A. Bruijn,, M. E. Paape,, E. Schrama,, L. A. van Es,, and F. J. van der Woude. 1992. IL-1 alpha stimulated TNF alpha production by cultured human proximal tubular epithelial cells. Kidney Int. 42: 383– 389.

116. Ye, G.,, C. Barrera,, X. Fan,, W. K. Gourley,, S. E. Crowe,, P. B. Ernst,, and V. E. Reyes. 1997. Expression of B7-1 and B7-2 costimulatory molecules by human gastric epithelial cells: potential role in CD4+ T cell activation during Helicobacter pylori infection. J. Clin. Invest. 99: 1628– 1636.

117. Zaidi, T. S.,, J. Lyczak,, M. Preston,, and G. B. Pier. 1999. Cystic fibrosis transmembrane conductance regulator-mediated corneal epithelial cell ingestion of Pseudomonas aeruginosa is a key component in the pathogenesis of experimental murine keratitis. Infect. Immun. 67: 1481– 1492.

118. Zar, H.,, L. Saiman,, L. Quittell,, and A. Prince. 1995. Binding of Pseudomonas aeruginosa to respiratory epithelial cells from patients with various mutations in the cystic fibrosis transmembrane regulator. J. Pediatr. 126: 230– 233.