Cellular Biology of Listeria monocytogenes Infection

Daniel A. Portnoy

doi:10.1128/9781555818340.ch18

Chapter 18 : Cellular Biology of Listeria monocytogenes Infection

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Affiliations: 1: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076

Content Type: Monograph

Publication Year: 1994

Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis

Book DOI: 10.1128/9781555818340

Chapter DOI: 10.1128/9781555818340.ch18

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Abstract:

In this chapter, the molecular and cellular biology of Listeria monocytogenes infection is reviewed and, at the end, a model which attempts to bridge the immunology with the pathogenesis is discussed. A number of factors facilitate in vitro assays. First, and most importantly, L. monocytogenes actually grows intracellularly. Second, gentamicin can be used to sterilize the extracellular medium without affecting the intracellular growth rate. Third, the infection of host cells is relatively nontoxic, so that cells do not detach from the substrate and gentamicin does not enter the cell cytoplasm. Lastly, the stages in the infection can be examined and quantitated by electron microscopy and video microscopy. The current model also has serious implications for the nature of antigen presentation. Current models describe two distinct pathways of antigen presentation. The first involves the processing of antigens within an acidic vacuolar compartment and presentation to CD4+ T cells in the context of major histocompatibility complex (MHC) class II antigens. The second involves presentation of cytosolic antigens and presentation to CD8+ T cells in the context of MHC class I antigens. Nevertheless, all mutants which enter the cytoplasm were shown to immunize mice to subsequent challenge. Thus, the data are consistent with the requirement that the organism must enter the cytoplasm for the induction of immunity. Whether entry into the cytoplasm is sufficient for long-lived immunity or whether cell-to-cell spread is also necessary remains to be determined.

Citation: Portnoy D. 1994. Cellular Biology of Listeria monocytogenes Infection, p 279-293. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch18

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Cellular Biology of Listeria monocytogenes Infection

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Figure 1

Model for the intracellular life cycle of L. monocytogenes. The stippled material represents polymerized actin. Adapted from Tilney and Portnoy ( 105 ), with copyright permission of the Rockefeller University Press.

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Figure 1

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Figure 2

prfA regulon of L. monocytogenes. Genes are represented by large arrows, transcripts are represented by wavy lines, putative PrfA-binding sites are represented by small boxes containing short arrows, and putative rho-independent terminators are represented by a short post terminated by a circle. PrfA protein is shown as a dimer, although this has not been demonstrated. This model is based on information presented in previous publications ( 15 , 16 , 31 , 32 , 55 , 56 , 62 , 63 , 108 ).

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Figure 2

References

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1. Alouf, J. E.,, and C. Geoffroy. 1991. The family of the antigenically-related, cholesterol-binding ('sulphydryl-activated') cytolytic toxins, p. 147– 186. In J. E. Alouf, and J. H. Freer (ed.), Sourcebook of Bacterial Protein Toxins. Academic Press, London.

2. Bancroft, G. J.,, M. J. Bosma,, G. C. Bosma,, and E. R. Unanue. 1986. Regulation of macrophage la expression in mice with severe immunodeficiency: induction of la expression by a T cell-independent mechanism. J. Immunol. 137: 4– 9.

3. Barry, R. A.,, H. G. A. Bouwer,, D. A. Portnoy,, and D. J. Hinrichs. 1992. Pathogenicity and immunogenicity of Listeria monocytogenes small-plaque mutants defective for intracellular growth and ceil-to-cell spread. Infect. Immun. 60: 1625– 1632.

4. Berche, P.,, J. Gaillard,, and P. J. Sansonetti. 1987. Intracellular growth oí Listeria monocytogenes as a prerequisite for in vivo induction of T cell-mediated immunity. J. Immunol. 138: 2266– 2271.

5. Bernardin!, M. L.,, J. Mounier,, H. d'Hauterville,, M. Coquis-Rondon,, and P. J. Sansonetti. 1989. icsA, a plasmid locus of Shigella flexneri, governs bacterial intra- and intercellular spread through interaction with F-actin. Proc. Natl. Acad. Sci. USA 86: 3867– 3871.

6. Bielecki, J.,, P. Youngman,, P. Connelly,, and D. A. Portnoy. 1990. Bacillus subtilis expressing a haemolysin gene from Listeria monocytogenes can grow in mammlian cells. Nature (London) 345: 175– 176.

7. Bishop, D. K.,, and D. J. Hinrichs. 1987. Adoptive transfer of immunity to Listeria monocytogenes: the influence of in vitro stimulation on lymphocyte subset requirements. J. Immunol. 139: 2005– 2009.

8. Blanden, R. V.,, and R. E.. Langman. 1972. Cell-mediated immunity to bacterial infection in the mouse. Thymus-derived cells as effectors of acquired resistance to Listeria monocytogenes. Scand. J. Immunol. 1: 379– 391.

9. Bouwer, H. G. A.,, C. S. Nelson,, B. L. Glbbins,, D. A. Portnoy,, and D. J. Hinrichs. 1992. Listeriolysin O is a target of the immune response to Listeria monocytogenes. J. Exp. Med. 175: 1467– 1471.

10. Brundage, R. A.,, G. A. Smith,, A. Camilli,, J. A. Theriot,, and D. A. Portnoy. 1993. Expression and phosphorylation of the Listeria monocytogenes ActA protein in mammalian cells. Proc. Natl. Acad. Sci. USA 90: 11890– 11894.

11. Brunt, L. M.,, D. A. Portnoy,, and E. R. Unanue. 1990. Presentation oí Listeria by CD8 + T cells requires secretion of hemolysin and intracellular growth. J. Immunol. 145: 3540– 3546.

12. Cambell, P. A. 1986. Are inflammatory phagocytes responsible for resistance to facultative intracellular bacteria? Immunol. Today 7: 70– 72.

13. Camilli, A.,, C. R. Paynton,, and D. A. Portnoy. 1989. Intracellular methicillin selection of Listeria monocytogenes mutants unable to replicate in a macrophage cell line. Proc. Natl. Acad. Sci. USA 86: 5522– 5526.

14. Camilli, A.,, D. A. Portnoy,, and P. Youngman. 1990. Insertional mutagenesis of Listeria monocytogenes with a novel Tn 917 derivative that allows direct cloning of DNA flanking transposon insertions. J Bacteriol. 172: 3738– 3744.

15. Camilli, A.,, L. G. Tilney,, and D. A. Portnoy. 1993. Dual roles of pIcA in Listeria monocytogenes pathogenesis. Mol. Microbiol. 8: 143– 157.

16. Chakraborty, T.,, M. Leimeister-Wachter,, E. Domann,, M. Hartl,, W. Goebel,, T. Nichterlein,, and S. Notermans. 1992. Coordinate regulation of virulence genes in Listeria monocytogenes requires the product of the prfA gene. J. Bacteriol. 174: 568– 574.

17.Cheers, C, and R. Waller. 1975. Activated macrophages in congenitally athymic "nude" mice and in lethally irradiated mice. J. Immunol. 115: 844– 847.

18. Conlan, J. W.,, and R. J. North. 1991. Neutrophil-mediated dissolution of infected host cells as a defense strategy against a facultative intracellular bacterium. J. Exp. Med. 174: 741– 744.

19. Conlan, J. W.,, and R. J. North. 1992. Early pathogenesis of infection in the liver with the facultative intracellular bacteria Listeria monocytogenes, Francisella tularensis, and Salmonella typhimurium involves lysis of infected hepatocytes by leukocytes. Infect. Immun. 60: 5164– 5171.

20. Cossart, P.,, M. F. Vincente,, J. Mengaud,, F. Baquero,, J. C. Perez-Diaz,, and P. Berche. 1989. Listeriolysin O is essential for virulence of Listeria monocytogenes: direct evidence obtained by gene complementation. Infect. Immun. 57: 3629– 3636.

21. Dabiri, G. A.,, J. M. Sanger,, D. A. Portnoy,, and F. S. South wick. 1990. Listeria monocytogenes moves rapidly through the host cytoplasm by inducing directional actin assembly. Proc. Natl. Acad. Sci. USA 87: 6068– 6072.

22. De Libero, G.,, and S. H. E. Kaufmann. 1986. Antigen-specific Lyt-2 + lymphocytes from mice infected with the intracellular bacterium Listeria monocytogenes. J. Immunol. 137: 2688– 2694.

23. 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.

24. Domann, E.,, J. Wehland,, M. Rohde,, S. Pistor,, M. Hartl,, W. Goebel,, M. Leimeister-Wachter,, M. Wuenscher,, and T. Chakraborty. 1992. A novel bacterial virulence gene in Listeria monocytegenes required for host cell microfilament interaction with homology to the proline-rich region of vinculin. EMBOJ. 11: 1981– 1990.

25. Drevets, D. A.,, and P. A. Campbell. 1991. Roles of complement and complement receptor type 3 in phagocytosis of Listeria monocytogenes by inflammatory mouse peritoneal macrophages. Infect. Immun. 59: 2645– 2652.

26. Drevets, D. A.,, B. P. Canono,, and P. A. Campbell. 1992. Listericidal and nonlistericidal mouse macrophages differ in complement receptor type 3-mediated phagocytosis of L. monocytogenes and in preventing escape of the bacteria into the cytoplasm. J. Leukocyte Biol. 52: 70– 79.

27. Dunn, P. L.,, and R. J. North. 1991. Early gamma interferon production by natural killer cells is important in defense against murine listeriosis. Infect. Immun. 59: 2892– 2900.

28. Emmerling, P.,, H. Finger,, and H. Hof. 1977. Cell-mediated resistance to infection with Listeria monocytogenes in nude mice. Infect. Immun. 15: 382– 385.

29. Farber, J. M.,, and P. I. Peterkin. 1991. Listeria monocytogenes, a food-borne pathogen. Microbiol. Rev. 55: 476– 511.

30. Fischetti, V. A.,, V. Pancholi,, and O. Schneewind. 1990. Conservation of a hexapeptide sequence in the anchor region of surface proteins from gram-positive cocci. Mol. Microbiol. 4: 1603– 1605.

31. Freitag, N. E.,, L. Rong,, and D. A. Portnoy. 1993. Regulation of the prfA transcriptional activator of Listeria monocytogenes: multiple promoter elements contribute to intracellular growth and cell-to-cell spread. Infect. Immun. 61: 2537– 2544.

32. Freitag, N. E.,, P. Yongman,, and D. A. Portnoy. 1992. Transcriptional activation of the Listeria monocytogenes hemolysin gene in Bacillus subtilis. J. Bacteriol. 174: 1293– 1298.

33. Gaillard, J. L.,, P. Berche,, C. Frebel,, E. Gouin,, and P. Cossart. 1991. Entry of L. monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from gram-positive cocci. Cell 65: 1127– 1141.

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

35. Gaillard, J. L.,, P. Berche,, and P. Sansonetti. 1986. Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes. Infect. Immun. 52: 50– 55.

36. Gellin, B. G., and C. V. Broome. 1989. Listeriosis. JAMA 261: 1313– 1320.

37. Geoffroy, C.,, J. L. Gaillard,, J. E. Alouf,, and P. Berche. 1987. Purification, characterization, and toxicity of the sulfhydryl-activated hemolysin listeriolysin O from Listeria monocytogenes. Infect. Immun. 55: 1641– 1646.

38. Geoffroy, C.,, J. Raveneau,, J. Beretti,, A. Lecroisey,, J.-A. Vazques-Boland,, J. E. Alouf,, and P. Berche. 1991. Purification and characterization of an extracellular 29-kilodalton phospholipase C from Listeria monocytogenes. Infect. Immun. 59: 2382– 2388.

39. Goldberg, M. B.,, and P. J. Sansonetti. 1993. Shigella subversion of the cellular cytoskeleton: a strategy for epithelial colonization. Infect. Immun. 61: 4941– 4946.

40. Goldflne, H.,, N. C. Johnston,, and C. Knob. 1993. The nonspecific phospholipase O of Listeria monocytogenes: activity on phospholipids in Triton X-100 mixed micelles and in biological membranes. J. Bacteriol. 175: 4298– 4306.

41. Havell, E. A. 1986. Synthesis and secretion of interferon by murine fibroblasts in response to intracellular Listeria monocytogenes. Infect. Immun. 54: 787– 792.

42. Heinzen, R. A.,, S. F. Hayes,, M. G. Peacock,, and T. Hackstadt. 1993. Directional actin polymerization associated with spotted fever group rickettsia infection of Vero cells. Infect. Immun. 61: 1926– 1935.

43. Hsieh, C.-S.,, S. E. Macatonia,, C. S. Tripp,, S. F. Wolf,, A. O'Garra, and K. M. Murphy. 1993. Development of TH1 CD4 + T cells through IL-12 produced by Listeria-induced macrophages. Science 260: 547– 549.

44. Huang, S.,, W. Hendriks,, A. Althage,, S. Hemmi,, H. Bluethmann,, R. Kanujo,, J. Vilcek,, R. M. Zinkernagel,, and M. Aguet. 1993. Immune responses in mice that lack the interferon-γ receptor. Science 259: 1742– 1745.

45. Jones, S.,, and D. A. Portnoy. Unpublished data.

46. Joris, B.,, S. Englebert,, C.-P. Chu,, R. Kariyama,, L. Daneo-Moore,, G. D. Shockman,, and J.-M. Ghuysen. 1992. Modular design of the Enterococcus hirae muramidase-2 and Streptococcus fae-calis autolysin. FEMS Microbiol. Lett. 91: 257– 264.

47. Kathariou, S.,, P. Metz,, H. Hof,, and W. Goebel. 1987. Tn 916-induced mutations in the hemolysin determinant affecting virulence of Listeria monocytogenes. J. Bacteriol. 169: 1291– 1297.

48. Kaufmann, S. H. E. 1993. Immunity to intracellular bacteria. Annu. Rev. Immunol. 11: 129– 163.

49. Kocks, C.,, E. Gouin,, M. Tabouret,, P. Berche,, H. Ohayon,, and P. Cossart. 1992. L. monocyto-gertes-induced actin assembly requires the actA gene product, a surface protein. Cell 68: 521– 531.

50. Kocks, C.,, R. Hellio,, P. Gounon,, H. Ohayon,, and P. Cossart. 1993. Polarized distribution of Listeria monocytogenes surface protein ActA at the site of directional actin assembly. J. Cell Sci. 105: 699– 710.

51. Kuhn, M.,, and W. Goebel. 1989. Identification of an extracellular protein of Listeria monocytogenes possibly involved in intracellular uptake by mammalian cells. Infect. Immun. 57: 55– 61.

52. Kuhn, M.,, S. Kathariou,, and W. Goebel. 1988. Hemolysin supports survival but not entry of the intracellular bacterium Listeria monocytogenes. Infect. Immun. 56: 79– 82.

53. Kuhn, M.,, M. C. Prévost,, J. Mounier,, and P. J. Sansonetti. 1990. A nonvirulent mutant of Listeria monocytogenes does not move intracellular^ but still induces polymerization of actin. Infect. Immun. 58: 3477– 3486.

54. Lane, F. C.,, and E. R. Unanue. 1972. Requirement of thymus (T) lymphocytes for resistance to listeriosis. J. Exp. Med. 135: 1104– 1112.

55. Leimeister-Wachter, M.,, E. Domann,, and T. Chakraborty. 1992. The expression of virulence in Listeria monocytogenes is thermoregulated. J. Bacteriol. 174: 947– 952.

56. Leimeister-Wachter, M.,, C. Haffner,, E. Domann,, W. Goebel,, and T. Chakraborty. 1990. Identification of a gene that positively regulates expression of listeriolysin, the major virulence factor of Listeria monocytogenes. Proc. Natl. Acad. Sci. USA 87: 8336– 8340.

57. MacDonald, T. T.,, and P. B. Carter. 1980. Cell-mediated immunity to intestinal infection. Infect. Immun. 28: 516– 523.

58. Mackaness, G. B. 1962. Cellular resistance to infection. J. Exp. Med. 116: 381– 406.

59. Mackaness, G. B. 1964. The immunological basis of acquired cellular resistance. J. Exp. Med. 120: 105– 120.

60. Marquis, H.,, H. G. A. Bouwer,, D. J. Hinrichs,, and D. A. Portnoy. 1993. Intracytoplasmic growth and virulence of Listeria monocytogenes auxotrophic mutants. Infect. Immun. 61: 3756– 3760.

61. Marquis, H.,, and D. A. Portnoy. Unpublished data.

62. Mengaud, J.,, S. Dramsi,, E. Gouin,, J. A. Vazquez-boland,, G. Milon,, and P. Cossart. 1991. Pleiotro-pic control of Listeria monocytogenes virulence factors by a gene that is autoregulated. Mol. Microbiol. 5: 2273– 2283.

63. Mengaud, J.,, M. F. Vicente,, and P. Cossart. 1989. Transcriptional mapping and nucleotide sequence of the Listeria monocytogenes MyA region reveal structural features that may be involved in regulation. Infect. Immun. 57: 3695– 3701.

64. Michel, E.,, and P. Cossart. 1992. Physical map of the Listeria monocytogenes chromosome. J. Bacteriol. 174: 7098– 7103.

65. Michel, E.,, K. A. Reich,, R. Favier,, P. Berche,, and P. Cossart. 1990. Attenuated mutants of the intracellular bacterium Listeria monocytogenes obtained by single amino acid substitutions in listeriolysin O. Mol. Microbiol. 4: 2167– 2178.

66. Mielke, M. E. A.,, G. Niedobitek,, H. Stein,, and H. Hahn. 1989. Acquired resistance to Listeria monocytogenes is mediated by Lyt-2 + T cells independently of the influx of monocytes into granulomatous lesions. J. Exp. Med. 170: 589– 594.

67. Mombaerts, P.,, J. Arnold!,, F. Russ,, S. Tonegawa,, and S. H. E. Kaufmann. 1993. Different roles of afi and 78 T cells in immunity against an intracellular bacterial pathogen. Nature (London) 365: 53– 56.

68. 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.

69. Newborg, M. F.,, and R. J. North. 1980. The mechanism of T cell independent anti-Lw/eria resistance in nude mice. J. Immunol. 124: 571– 576.

70. Nickol, A. D.,, and P. F. Bonventre. 1977. Anomalous high native resistance of athymic mice to bacterial pathogens. Infect. Immun. 18: 636– 645.

71. Niebuhr, K.,, T. Chakraborty,, M. Rohde,, T. Gazlig,, B. Jansen,, P. Kollner,, and J. Wehland. 1993. Localization of the ActA polypeptide of Listeria monocytogenes in infected tissue culture cell lines: ActA is not associated with actin "comets." Infect. Immun. 61: 2793– 2802.

72. North, R. J. 1970. The relative importance of blood monocytes and fixed macrophages to the expression of cell-mediated immunity to infection. J. Exp. Med. 132: 521– 534.

73. North, R. J. 1973. Cellular mediators of mli-Listeria immunity as an enlarged population of short-lived replicating T cells. Kinetics of their production. J. Exp. Med. 138: 342– 355.

74. North, R. J. 1975. Nature of "memory" in T-cell-mediated antibacterial immunity: anamnestic production of mediator T cells. Infect. Immun. 12: 754– 760.

75. North, R. J. 1978. The concept of the activated macrophage. J. Immunol. 121: 806– 809.

76. Pal, T.,, J. W. Newland,, B. D. Tall,, S. B. Formal,, and T. L. Hale. 1989. Intracellular spread of Shigella fiexneri associated with the kcpA locus and a 140-kilodalton protein. Infect. Immun. 57: 477– 486.

77. Pâmer, E. G. 1993. Cellular immunity to intracellular bacteria. Curr. Opin. Immunol. 5: 492– 496.

78. Pâmer, E. G.,, J. T. Harty,, and M. J. Bevan. 1991. Precise prediction of a dominant class IMHC-restricted epitope of Listeria monocytogenes. Nature (London) 353: 852– 855.

79. Park, S. F.,, and S. A. B. Stewart. 1990. High-efficiency transformation of Listeria monocytogenes by electroporation of penicillin-treated cells. Gene 94: 129– 132.

80. Pfeffer, K.,, T. Matsuyama,, T. M. Kundig,, A. Wakeham,, K. Kishihara,, A. Shahinian,, K. Wieg-mann,, P. S. Ohashi,, M. Kronke,, and T. W. Mak. 1993. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock yet succumb to L. monotogenes infection. Cell 73: 457– 467.

81. Pinkney, M.,, E. Beachey,, and M. Kehoe. 1989. The thiol-activated toxin streptolysin O does not require a thiol group for cytolytic activity. Infect. Immun. 57: 2553– 2558.

82. Portnoy, D. A. 1992. Innate immunity to a facultative intracellular bacterial pathogen. Curr. Opin. Immunol. 4: 20– 24.

83. Portnoy, D. A.,, T. Chakraborty,, W. Goebel,, and P. Cossart. 1992. Molecular determinants of Listeria monocytogenes pathogenesis. Infect. Immun. 60: 1263– 1267.

84. Portnoy, D. A.,, P. S. Jacks,, and D. J. Hinrichs. 1988. Role of hemolysin for the intracellular growth of Listeria monocytogenes. J. Exp. Med. 167: 1459– 1471.

85. Portnoy, D. A.,, R. D. Schreiber,, P. Connelly,, and L. G. Tilney. 1989. Gamma interferon limits access of Listeria monocytogenes to the macrophage cytoplasm. J. Exp. Med. 170: 2141– 2146.

86. Portnoy, D. A.,, R. K. Tweten,, M. Kehoe,, and J. Bielecki. 1992. Capacity of listeriolysin O, streptolysin O, and perfringolysin O to mediate growth of Bacillus subtilis within mammalian cells. Infect. Immun. 60: 2710– 2717.

87. Poyart, C.,, E. Abachin,, I. Razaflmanantsoa,, and P. Berche. 1993. The zinc metalloprotease of Listeria monocytogenes is required for maturation of phosphatidylcholine phospholipase C: direct evidence obtained by gene complementation. Infect. Immun. 61: 1576– 1580.

88. Racz, P.,, K. Tenner,, and E. Mero. 1972. Experimental Listeria enteritis. I. An electron microscopic study of the epithelial phase in experimental Listeria infection. Lab. Invest. 26: 694– 700.

89. Roberts, A. D.,, D. J. Ordway,, and I. M. Orme. 1993. Listeria monocytogenes infection in β2 microglobulin-deficient mice. Infect. Immun. 61: 1113– 1116.

90. Rogers, H. W.,, and E. R. Unanue. 1993. Neutrophils are involved in acute, nonspecific resistance to Listeria monocytogenes in mice. Infect. Immun. 61: 5090– 5096.

91. Rosen, H.,, S. Gordon,, and R. J. North. 1989. Exacerbation of murine listeriosis by a monoclonal antibody specific for the type 3 complement receptor of myelomonocytic cells. Absence of monocytes at infective foci allows Listeria to multiply in nonphagocytic cells. J. Exp. Med. 170: 27– 37.

92. Rothe, J.,, W. Lesslauer,, H. Lotscher,, V. Lang,, P. Koebel,, F. Kontgen,, A. Althage,, R. Zinkernagel,, M. Steinmetz,, and H. Bluethmann. 1993. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature (London) 364: 798– 802.

93. Sanger, J. M.,, J. W. Sanger,, and F. S. Southwick. 1992. Host cell actin assembly is necessary and likely to provide the propulsive force for intracellular movement of Listeria monocytogenes. Infect. Immun. 60: 3609– 3619.

94. Smith, G. A.,, and D. A. Portnoy. Unpublished data.

95. Smyth, C. J.,, and J. L. Duncan,. 1978. Thiol-activated (oxygen-labile) cytolysins. In J. Jeljaszewicz, and T. Wasstrom (ed.), Bacterial Toxins and Cell Membranes. Academic Press, Inc., New York.

96. Stevens, D. L.,, J. Mitten,, and C. Henry. 1987. Effects of a and 9 toxins from Clostridium perfringens on human polymorphonuclear leukocytes. J. Infect. Dis. 156: 324– 333.

97. Sun, A. N.,, A. Camilli,, and D. A. Portnoy. 1990. Isolation of Listeria monocytogenes small-plaque mutants defective for intracellular growth and cell-to-cell spread. Infect. Immun. 58: 3770– 3778.

98. Tanaka, M.,, and H. Shibata. 1985. Poly (L-proline)-binding proteins from chick embryos are profilin and profilactin. Eur. J. Biochem. 151: 291– 297.

99. Teysseire, N.,, C. Chiche-Portiche,, and D. Raoult. 1992. Intracellular movements of Rickettsia conorii and R. typhi based on actin polymerization. Res. Microbiol. 143: 821– 829.

100. Theriot, J. A.,, and T. J. Mitchison. 1993. The three faces of profilin. Cell 75: 835– 838.

101. Theriot, J. A.,, T. J. Mitchison,, L. G. Tilney,, and D. A. Portnoy. 1992. The rate of actin-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization. Nature (London) 357: 257– 260.

102. Theriot, J. A.,, J. Rosenblatt,, D. A. Portnoy,, P. J. Goldschmidt-Clermont,, and T. J. Mitchison. 1994. Involvement of profilin in the actin-based motility of Listeria monocytogenes in cells and in cell-free extracts. Cell 74: 505– 517.

103. Tilney, L. G.,, P. S. Connelly,, and D. A. Portnoy. 1990. The nucleation of actin filaments by the bacterial intracellular pathogen, Listeria monocytogenes. J. Cell Biol. 111: 2979– 2988.

104. Tilney, L. G.,, D. J. DeRosier,, A. Weber,, and M. S. Tilney. 1992. How Listeria exploits host cell actin to form its own cytoskeleton. II. Nucleation, actin filament polarity, filament assembly, and evidence for a pointed end capper. J. Cell Biol. 118: 83– 93.

105. Tilney, L. G.,, and D. A. Portnoy. 1989. Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J. Cell Biol. 109: 1597– 1608.

106. Titball, R. W. 1993. Bacterial phospholipases C. Microbiol. Rev. 57: 347– 366.

107. Van Epps, D. E.,, and B. R. Andersen. 1974. Streptolysin O inhibition of neutrophil chemotaxis and mobility: nonimmune phenomenon with species specificity. Infect. Immun. 9: 27– 33.

108. Vazquez-Boland, J.-A.,, C. Kocks,, S. Dramsi,, H. Ohayon,, C. Geoffrey,, J. Mengaud,, and P. Cossart. 1992. Nucleotide sequence of the lecithinase operon of Listeria monocytogenes and possible role of lecithinase in cell-to-cell spread. Infect. Immun. 60: 219– 230.

109. von Koenig, C. H. W.,, H. Finger,, and H. Hof. 1982. Failure of killed Listeria monocytogenes vaccine to produce protective immunity. Nature (London) 297: 233– 234.

110. Wuenscher, M. D.,, S. Kohier,, W. Goebel,, and T. Chakraborty. 1991. Gene disruption by plasmid integration in Listeria monocytogenes: insertional inactivation of the listeriolysin determinant UsA. Mol. Gen. Genet. 228: 177– 182.

111. Yewdell, J. W.,, and J. R. Bennink. 1990. The binary logic of antigen processing and presentation to T cells. Cell 62: 203– 206.

112. Zachar, Z.,, and D. C. Savage. 1979. Microbial interference and colonization of the murine gastrointestinal tract by Listeria monocytogenes. Infect. Immun. 23: 168– 174.