The Role of Granulocytes, Naive and Activated Macrophages in the Host Resistance against Salmonella typhimurium

  • Ralph van Furth
  • Jaap T. van Dissel
  • Jan A. M. Langermans
Part of the NATO ASI Series book series (NSSA, volume 245)


Mononuclear phagoytes play an important role in the innate resistance of mice against infection by Salmonella typhimurium. The outcome of an infection is influenced by a number of factors, ranging from the handling of the microorganisms by resident macrophages during the earliest phase of infection to the appearance of specific cellular and humoral immune responses in a later phase. Control of the rate of proliferation of S. typhimurium in the liver and spleen of mice during the first week of infection is the earliest process known to be genetically determined (Plant and Glynn, 1976; Hormeache, 1979; Hormeache, 1980a; Skamene et al., 1982). On the basis of the differences in the early in vivo outgrowth, inbred mice can be divided into resistant and susceptible strains. in vivo studies have indicated that the control of S. typhimurium proliferation is due to an inherent property of macrophages (Robson and Vas, 1972; Maier and Oels, 1972; Vas, 1978; O’Brien et al., 1979; Hormaeche et al., 1980b; O’Brien and Metcalf, 1982). Our studies showed no difference in the phagocytic ability of peritoneal macrophages from resistant CBA and susceptible C57BL/10 mice for S. typhimurium opsonized with immune serum, but we found that the initial rate of intracellular killing of ingested S. typhimurium by CBA macrophages was more rapid than by macrophages from C57BL/10 mice (Van Dissel et al., 1985), which reflects the constitutive difference between the two strains of mice. However, equal rates of intracellular killing of L. monocytogenes were found for macrophages from the Listeria-susceptible CBA mice and the Listeria-resistant C57BL/10 mice (Van Dissel et al., 1985), which indicates that other factors do well influence the outcome of infections with these bacteria. Such a factor could be the greater number of monocyte-derived exudate macrophages in the inflammatory exudate in C57BL/10 mice than in CBA mice (Stevenson et al., 1981; Sluiter et al., 1984), which is due to a difference in the response to the factor-increasing monocytopoiesis (Sluiter et al., 1984).


Peritoneal Macrophage Inbred Mouse Purify Protein Derivative Resident Macrophage Natural Resistance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Blanden, R.V., Lefford, M.J., and Mackaness, G.B., 1969, The host response to Calmette-Guérin bacillus infection in mice, J. Exp. Med. 129:1079.PubMedCrossRefGoogle Scholar
  2. Collins, F.M., 1974, Vaccines and cell-mediated immunity, Bacteriol Rev. 38:371.PubMedGoogle Scholar
  3. Crocker, P.R., Blackwell, J.M., and Bradley, D.J., 1984, Expression of the natural resistance gene Lsh in resident liver macrophages, Infect. Immun. 43:1033.PubMedGoogle Scholar
  4. Eisenhower, P., Mack, D.G., and Mcleod, R., 1988, Prevention of peroral and congeital acquisition of Toxoplasma gondii by antibody and activated macrophages, Infect. Immun. 56:83.Google Scholar
  5. Garcia-Penarrubia, P., Koster, F.T., Kelley, R.O., McDowell, T.D., and Bankhurst, A.D., 1989, Antibacterial activity of natural killer cells, J. Exp. Med. 169:99.PubMedCrossRefGoogle Scholar
  6. Hiemstra, P.S., Eisenhauer, P.B., Harwig, S.S.L., Van den Barselaar, M.Th., Van Furth, R., and Lehrer, R.I., Identification of major proteins with broad spectrum antimicrobial activity in murine macrophages, (submitted for publication).Google Scholar
  7. Hoff, R., 1975, Killing in vitro of Trypanosoma cruzi by macrophages from mice immunized with T. cruzi or BCG, and absence of cross-immunity on challenge in vivo, J. Exp. Med. 142:299.PubMedCrossRefGoogle Scholar
  8. Hormeache, C.E., 1979, Natural resistance to Salmonella typhimurium in different inbred strains of mice, Immunology 37:311.Google Scholar
  9. Hormaeche, C.E., 1980a, The in vivo division and death rates of Salmonella typhimurium in the spleens of naturally resistant and susceptible mice measured by the superinfecting phage technique of Meynell, Immunology 41:973.PubMedGoogle Scholar
  10. Hormaeche, C.E., Brock, J., and Pettifor, P., 1980b, Natural resistance to mouse typhoid:possible role for the macrophage, in: “Genetic control of natural resistance to infection and Malignancy”, E. Skamene, P.A.L. Kongshavn, and M. Landy, ed., Academic Press, New York.Google Scholar
  11. Langermans, J.A.M., Van der Hulst, M.E.B., Nibbering, P.H., and Van Furth, R., 1990, Activation of mouse peritoneal macrophages during infection with Salmonella typhimurium does not result in enhanced intracellular killing, J. Immunol. 144:4340.PubMedGoogle Scholar
  12. Koerner, T.J., Hamilton, T.A., and Adams, D.O., 1987, Suppressed expression of surface Ia on macrophages by lipopolysaccharide: evidence for regulation at the leve of accumulation of mRNA. J. Immunol. 139:239.PubMedGoogle Scholar
  13. Langermans, J.A.M., Nibbering, P.H., Van der Hulst, M.E.B., and Van Furth, R., 1991, Microbicidal activities of Salmonella typhimurium-and interferon-gamma-activated mouse peritoneal macrophages, Pathobiology 59:189.PubMedCrossRefGoogle Scholar
  14. Langermans, J.A.M., Van der Hulst, M.E.B., Nibbering, P.H., Van der Meide, P.H., and Van Furth, R., 1992, Intravenous injection of IFN-β-induced L-arginine-dependent toxoplasmastatic activity in murine peritoneal macrophages is mediated by endogenous tumor necrosis factor-α. J. Immunol. 148:568.PubMedGoogle Scholar
  15. Lissner, C.R., Swanson, R.N., and O’Brien, A.D., 1983, Genetic control of the innate resistance of mice to Salmonella typhimurium: expression of the Ity gene in peritoneal and splenic macrophages isolated in vitro, J. Immunol. 131:3006.PubMedGoogle Scholar
  16. Lissner, C.R., Weinstein, D.L., and O’Brien, A.D., 1985, Mouse chromosome 1 Ity locus regulates microbicidal activity of isolated peritoneal macrophages against a diverse group of intracellular and extracellular bacteria, J. Immunol. 135:544.PubMedGoogle Scholar
  17. Mackaness, G.B., 1964, The immunological basis of acquired cellular resistance, J. Exp. Med. 120:105.PubMedCrossRefGoogle Scholar
  18. Mackaness, G.B., Blanden, R.V., and Collins, F.M., 1966, Hostparasite relations in mouse typhoid. J. Exp. Med. 124:573.PubMedCrossRefGoogle Scholar
  19. Mackaness, G.B., 1971, Resistance to intracellular infection, J. Infect. Dis. 123:439.PubMedCrossRefGoogle Scholar
  20. Maier, T., and Oels, H.C., 1972, Role of the macrophage in natural resistance to Salmonellosis in mice, Infect. Immun. 6:438.PubMedGoogle Scholar
  21. Murray, H.W., and Cohn, Z.A., 1980, Macrophage oxygen-dependent antimicrobial activity. III. Enhancate metabolism as an expression of macrophage activation, J. Exp. Med. 152:1596.PubMedCrossRefGoogle Scholar
  22. Murray, H.W., Spitalny, G.L., and Nathan, C.F., 1985, Activation of mouse peritoneal macrophages in vitro and in vivo by interferon-γ, J. Immunol. 134:1619.PubMedGoogle Scholar
  23. Nakoneczna, I., and Hsu, H.S., 1980, The comparative histopathology of primary and secondary lesions in murine salmonellosis, Br. J. Exp. Pathol. 61:76.PubMedGoogle Scholar
  24. Nathan, C.F., Murray, H.W., and Cohn, Z.A., 1980, The macrophage as an effector cell, N. Engl. J. Med. 303:622.PubMedCrossRefGoogle Scholar
  25. Nibbering, P.H., Langermans, J.A.M., Van de Gevel, J.S., Van der Hulst, M.E.B., and Van Furth, R., 1991, Nitrite production by activated murine macrophages correlates with their toxoplasmastatic activity, Ia antigen expression, and production of H2O2 Immunobiology 184:93.Google Scholar
  26. O’Brien, A.D., Scher, L, and Formai, S.B., 1979, Effect of silica on the innate resistance of inbred mice to Salmonella typhimurium infection, Infect. Immun. 25:513.PubMedGoogle Scholar
  27. O’Brien, A.D., and Metcalf, E.S., 1982, Control of early Salmonella typhimurium growth in innately Salmonella-resistant mice does not require functional T lymphocytes, J. Immunol. 129:1349.PubMedGoogle Scholar
  28. Pappas, M.P., and Nacy, C.A., 1983, Antileishmanial activities of macrophages from C3H/HeN and C3H/HeJ mice treated with Mycobacterium bovis strain BCG, Cell. Immunol. 80:217.PubMedCrossRefGoogle Scholar
  29. Plant, J., and Glynn, A.A., 1976, Genetics of resistance to infection with Salmonella typhimurium in mice, J. Infect. Dis. 133:72.PubMedCrossRefGoogle Scholar
  30. Plant, J.E., Blackwell, J.M., O’Brien, A.D., Bradley, D.J., and Glynn, A.A., 1982, Are the Lsh and Ity disease genes at one locus on mouse chromosome 1?, Nature 297:510.PubMedCrossRefGoogle Scholar
  31. Robson, H.G., and Vas, S.I., 1972, Resistance of inbred mice to Salmonella typhimurium, J. Infect. Dis. 126:378.PubMedCrossRefGoogle Scholar
  32. Ruco, L.P., and Meltzer, M.S., 1977, Macrophage activation for tumor cytotoxicity: induction of tumoricidal macrophages by PPD in BCG-immune mice, Cell. Immunol. 32:203.CrossRefGoogle Scholar
  33. Schafer, R., and Eisenstein, T.K., 1988, Induction of natural killer cell activity by a Salmonella vaccin. FASEB J. 2:A677.Google Scholar
  34. Skamene, E., Gros, P., Forget, A., Kongshavn, P.A.L., St.Charles, C., and Taylor, B.A., 1982, Genetic regulation of resistance to intracellular pathogens, Nature 297:506.PubMedCrossRefGoogle Scholar
  35. Stach, J.L., Gros, P., Forget, A., and Skamene, E., 1984, Phenotypic expression of genetically-controlled natural resistance to Mycobacterium bovis (BCG), J. Immunol. 132:888.PubMedGoogle Scholar
  36. Stevenson, M.M., Kongshavn, P.A.L., and Skamene, E., 1981, Genetic linkage of resistance to Listeria monocytogenes with macrophage inflammatory responses, J. Immunol. 127:402.PubMedGoogle Scholar
  37. Van Dissel, J.T., Leijh, P.C.J., and Van Furth, R., 1972, Differences in initial rate of intracellular killing of Salmonella typhimurium by resident peritoneal macrophages from various mouse strains, J. Immunol. 134:3404.Google Scholar
  38. Van Dissel, J.T., Stikkelbroeck, J.J.M., Sluiter, W., Leijh, P.C.J., and Van Furth, R., 1986, Differences in initial rate of intracellular killing of Salmonella typhimurium by granulocytes of Salmonella-susceptible C57BL/10 mice and Salmonella-resistant CBA mice, J. Immunol. 136:1074.PubMedGoogle Scholar
  39. Van Dissel, J.T., Stikkelbroeck, J.J.M., Michel, B.C., Leijh, P.C.J., and Van Furth, R., 1987a, Salmonella typhimurium-specific difference in rate of intracellular killing by resident peritoneal macrophages from Salmonella-resistant CBA and Salmonella-susceptible C57BL/10 mice, J. Immunol. 138:4428.PubMedGoogle Scholar
  40. Van Dissel, J.T., Stikkelbroeck, J.M., Van den Barselaar, M. Th., Sluiter, W., Leijh, P.C.J., and Van Furth, R., 1987b, Divergent changes in antimicrobial activity after immunologic activation of mouse peritoneal macrophages, J. Immunol. 139:1665.PubMedGoogle Scholar
  41. Van Dissel, J.T., Stikkelbroeck, J.J.M., Michel, B.C., Van den Barselaar, M.Th., Leijh, P.C.J., and Van Furth, R., 1987c, Inability of recombinant interferon-to activate the antibacterial activity of mouse peritoneal macrophages against Listeria monocytogenes and Salmonella typhimurium, J. Immunol. 139:1673.PubMedGoogle Scholar
  42. Vas, S.I., 1978, Genetic control of defenses against intracellular pathogens, in: “Infection Immunity, and Genetics”, H. Friedman, T.J. Linna, and J.E. Prier, eds., University Park Press, BaltimoGoogle Scholar
  43. Wang, X., Lin, F., Hsu, H.S., Mumaw, V.R., and Nakoneczna, I., 1988, Electronmicroscopic studies on the location of Salmonella proliferation in murine spleen, J. Med. Microbiol. 25:41.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Ralph van Furth
    • 1
  • Jaap T. van Dissel
    • 1
  • Jan A. M. Langermans
    • 1
  1. 1.Department of Infectious DiseasesUniversity Hospital LeidenLeidenThe Netherlands

Personalised recommendations