Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 Jan 1;179(1):259–268. doi: 10.1084/jem.179.1.259

Neutrophils are essential for early anti-Listeria defense in the liver, but not in the spleen or peritoneal cavity, as revealed by a granulocyte-depleting monoclonal antibody

PMCID: PMC2191333  PMID: 8270870

Abstract

This study shows that in mice selectively depleted of neutrophils by treatment with a monoclonal antibody, RB6-8C5, listeriosis is severely exacerbated in the liver, but not in the spleen or peritoneal cavity during the crucial first day of infection. At sites of infection in the livers of neutrophil-depleted mice, Listeria monocytogenes grew to large numbers inside hepatocytes. By contrast, in the livers of normal mice neutrophils rapidly accumulated at infectious foci and this was associated with the lysis of infected hepatocytes that served to abort infection in these permissive cells. In the spleen the situation was different, in that depletion of neutrophils did not result in appreciable exacerbation of infection. In this organ intact infected cells, many of which appeared to be fibroblast-like stromal cells, were found at foci of infection in the presence or absence of large numbers of neutrophils. This suggests that neutrophils are less effective at destroying L. monocytogenes-infected target cells in the spleen than in the liver. Consequently, at least during the first day, the organism remained free to multiply intracellularly in the spleen in cells that are permissive for its growth. Presumably, the same situation exists in the peritoneal cavity, because depleting neutrophils did not severely exacerbate infection initiated at this site.

Full Text

The Full Text of this article is available as a PDF (2.9 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Conlan J. W., Dunn P. L., North R. J. Leukocyte-mediated lysis of infected hepatocytes during listeriosis occurs in mice depleted of NK cells or CD4+ CD8+ Thy1.2+ T cells. Infect Immun. 1993 Jun;61(6):2703–2707. doi: 10.1128/iai.61.6.2703-2707.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Conlan J. W., North R. J. 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. 1992 Dec;60(12):5164–5171. doi: 10.1128/iai.60.12.5164-5171.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Conlan J. W., North R. J. Monoclonal antibody NIMP-R10 directed against the CD11b chain of the type 3 complement receptor can substitute for monoclonal antibody 5C6 to exacerbate listeriosis by preventing the focusing of myelomonocytic cells at infectious foci in the liver. J Leukoc Biol. 1992 Jul;52(1):130–132. doi: 10.1002/jlb.52.1.130. [DOI] [PubMed] [Google Scholar]
  4. Conlan J. W., North R. J. Neutrophil-mediated dissolution of infected host cells as a defense strategy against a facultative intracellular bacterium. J Exp Med. 1991 Sep 1;174(3):741–744. doi: 10.1084/jem.174.3.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Drevets D. A., Canono B. P., Campbell P. A. 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 Leukoc Biol. 1992 Jul;52(1):70–79. doi: 10.1002/jlb.52.1.70. [DOI] [PubMed] [Google Scholar]
  6. Dunn P. L., North R. J. Resolution of primary murine listeriosis and acquired resistance to lethal secondary infection can be mediated predominantly by Thy-1+ CD4- CD8- cells. J Infect Dis. 1991 Nov;164(5):869–877. doi: 10.1093/infdis/164.5.869. [DOI] [PubMed] [Google Scholar]
  7. Ferrante A., Carter R. F., Lopez A. F., Rowan-Kelly B., Hill N. L., Vadas M. A. Depression of immunity to Naegleria fowleri in mice by selective depletion of neutrophils with a monoclonal antibody. Infect Immun. 1988 Sep;56(9):2286–2291. doi: 10.1128/iai.56.9.2286-2291.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gaillard J. L., Berche P., Mounier J., Richard S., Sansonetti P. In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocyte-like cell line Caco-2. Infect Immun. 1987 Nov;55(11):2822–2829. doi: 10.1128/iai.55.11.2822-2829.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goossens P. L., Jouin H., Milon G. Dynamics of lymphocytes and inflammatory cells recruited in liver during murine listeriosis. A cytofluorimetric study. J Immunol. 1991 Nov 15;147(10):3514–3520. [PubMed] [Google Scholar]
  10. Hahn H., Kaufmann S. H. The role of cell-mediated immunity in bacterial infections. Rev Infect Dis. 1981 Nov-Dec;3(6):1221–1250. doi: 10.1093/clinids/3.6.1221. [DOI] [PubMed] [Google Scholar]
  11. Holmberg L. A., Ault K. A. Characterization of natural killer cells induced in the peritoneal exudates of mice infected with Listeria monocytogenes: a study of their tumor target specificity and their expression of murine differentiation antigens and human NK-associated antigens. Cell Immunol. 1984 Nov;89(1):151–168. doi: 10.1016/0008-8749(84)90206-5. [DOI] [PubMed] [Google Scholar]
  12. Mackaness G. B. The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med. 1969 May 1;129(5):973–992. doi: 10.1084/jem.129.5.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McFarland H. I., Nahill S. R., Maciaszek J. W., Welsh R. M. CD11b (Mac-1): a marker for CD8+ cytotoxic T cell activation and memory in virus infection. J Immunol. 1992 Aug 15;149(4):1326–1333. [PubMed] [Google Scholar]
  14. Mounier J., Ryter A., Coquis-Rondon M., Sansonetti P. J. Intracellular and cell-to-cell spread of Listeria monocytogenes involves interaction with F-actin in the enterocytelike cell line Caco-2. Infect Immun. 1990 Apr;58(4):1048–1058. doi: 10.1128/iai.58.4.1048-1058.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Portnoy D. A., Jacks P. S., Hinrichs D. J. Role of hemolysin for the intracellular growth of Listeria monocytogenes. J Exp Med. 1988 Apr 1;167(4):1459–1471. doi: 10.1084/jem.167.4.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rosen H., Gordon S., North R. J. 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. 1989 Jul 1;170(1):27–37. doi: 10.1084/jem.170.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rácz P., Tenner K., Mérö E. Experimental Listeria enteritis. I. An electron microscopic study of the epithelial phase in experimental listeria infection. Lab Invest. 1972 Jun;26(6):694–700. [PubMed] [Google Scholar]
  18. Rácz P., Tenner K., Szivessy K. Electron microscopic studies in experimental keratoconjunctivitis listeriosa. I. Penetration of Listeria monocytogenes into corneal epithelial cells. Acta Microbiol Acad Sci Hung. 1970;17(3):221–236. [PubMed] [Google Scholar]
  19. Sanger J. M., Sanger J. W., Southwick F. S. Host cell actin assembly is necessary and likely to provide the propulsive force for intracellular movement of Listeria monocytogenes. Infect Immun. 1992 Sep;60(9):3609–3619. doi: 10.1128/iai.60.9.3609-3619.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tepper R. I., Coffman R. L., Leder P. An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. Science. 1992 Jul 24;257(5069):548–551. doi: 10.1126/science.1636093. [DOI] [PubMed] [Google Scholar]
  21. Tilney L. G., Portnoy D. A. Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J Cell Biol. 1989 Oct;109(4 Pt 1):1597–1608. doi: 10.1083/jcb.109.4.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Winn R. K., Harlan J. M. CD18-independent neutrophil and mononuclear leukocyte emigration into the peritoneum of rabbits. J Clin Invest. 1993 Sep;92(3):1168–1173. doi: 10.1172/JCI116686. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES