Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1984 Mar;43(3):1033–1040. doi: 10.1128/iai.43.3.1033-1040.1984

Expression of the natural resistance gene Lsh in resident liver macrophages.

P R Crocker, J M Blackwell, D J Bradley
PMCID: PMC264289  PMID: 6698599

Abstract

Innate resistance and susceptibility to Leishmania donovani infection in mice is controlled by a single gene (Lsh) thought to be identical to the genes Ity and Bcg which control the early response to Salmonella typhimurium and Mycobacterium bovis infections, respectively. In the present study, three new aspects of Lsh gene activity were demonstrated. First, it was shown that liver macrophages continue to express Lsh gene activity in vitro after their extraction from mice infected in vivo, although 2 days of infection were required before the resistant phenotype was expressed. Second, detailed examination of early growth of the parasite and tritiated thymidine labeling of the parasites indicated that this delay in expression of the resistant phenotype also occurred in vivo. Third, the expression of resistance was unaltered by the effects of lethal irradiation but could be selectively enhanced by prior treatment with suitable doses of S. typhimurium lipopolysaccharide or L. donovani membranes. These results suggest that the resistance mechanism may be expressed by resident liver macrophages after their interaction with parasite-derived material. The relevance of these findings to the other intramacrophage pathogens is discussed.

Full text

PDF
1033

Selected References

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

  1. Bradley D. J., Kirkley J. Regulation of Leishmania populations within the host. I. the variable course of Leishmania donovani infections in mice. Clin Exp Immunol. 1977 Oct;30(1):119–129. [PMC free article] [PubMed] [Google Scholar]
  2. Bradley D. J., Kirkley J. Variation in susceptibility of mouse strains to Leishmania donovani infection. Trans R Soc Trop Med Hyg. 1972;66(4):527–528. [PubMed] [Google Scholar]
  3. Bradley D. J. Regulation of Leishmania populations within the host. IV. Parasite and host cell kinetics studied by radioisotope labelling. Acta Trop. 1979 Jun;36(2):171–179. [PubMed] [Google Scholar]
  4. Bradley D. J., Taylor B. A., Blackwell J., Evans E. P., Freeman J. Regulation of Leishmania populations within the host. III. Mapping of the locus controlling susceptibility to visceral leishmaniasis in the mouse. Clin Exp Immunol. 1979 Jul;37(1):7–14. [PMC free article] [PubMed] [Google Scholar]
  5. Bradley S. G. Cellular and molecular mechanisms of action of bacterial endotoxins. Annu Rev Microbiol. 1979;33:67–94. doi: 10.1146/annurev.mi.33.100179.000435. [DOI] [PubMed] [Google Scholar]
  6. Cluff L. E. Effects of endotoxins on susceptibility to infections. J Infect Dis. 1970 Sep;122(3):205–215. doi: 10.1093/infdis/122.3.205. [DOI] [PubMed] [Google Scholar]
  7. Crofton R. W., Diesselhoff-den Dulk M. M., van Furth R. The origin, kinetics, and characteristics of the Kupffer cells in the normal steady state. J Exp Med. 1978 Jul 1;148(1):1–17. doi: 10.1084/jem.148.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dwyer D. M. Isolation and partial characterization of surface membranes from Leishmania donovani promastigotes. J Protozool. 1980 May;27(2):176–182. doi: 10.1111/j.1550-7408.1980.tb04676.x. [DOI] [PubMed] [Google Scholar]
  9. Goldberg S. S., Cordeiro M. N., Silva Pereira A. A., Mares-Guia M. L. Release of lipopolysaccharide (LPS) from cell surface of Trypanosoma cruzi by EDTA. Int J Parasitol. 1983 Feb;13(1):11–18. doi: 10.1016/s0020-7519(83)80062-9. [DOI] [PubMed] [Google Scholar]
  10. Gottlieb M., Dwyer D. M. Leishmania donovani: surface membrane acid phosphatase activity of promastigotes. Exp Parasitol. 1981 Aug;52(1):117–128. doi: 10.1016/0014-4894(81)90067-9. [DOI] [PubMed] [Google Scholar]
  11. HOWARD J. G., ROWLEY D., WARDLAW A. C. Investigations on the mechanism of stimulation of non-specific immunity by bacterial lipopolysaccharides. Immunology. 1958 Jul;1(3):181–203. [PMC free article] [PubMed] [Google Scholar]
  12. Hormaeche C. E. 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. 1980 Dec;41(4):973–979. [PMC free article] [PubMed] [Google Scholar]
  13. Hormaeche C. E. The natural resistance of radiation chimeras to S. typhimurium C5. Immunology. 1979 Jun;37(2):329–332. [PMC free article] [PubMed] [Google Scholar]
  14. Kelly L. S., Dobson E. L. Evidence concerning the origin of liver macrophages. Br J Exp Pathol. 1971 Feb;52(1):88–99. [PMC free article] [PubMed] [Google Scholar]
  15. Ketteridge D. S. Lipopolysaccharide from Trypanosoma cruzi. Trans R Soc Trop Med Hyg. 1978;72(1):101–102. doi: 10.1016/0035-9203(78)90310-3. [DOI] [PubMed] [Google Scholar]
  16. O'Brien A. D., Metcalf E. S. Control of early Salmonella typhimurium growth in innately Salmonella-resistant mice does not require functional T lymphocytes. J Immunol. 1982 Oct;129(4):1349–1351. [PubMed] [Google Scholar]
  17. O'Brien A. D., Scher I., Formal S. B. Effect of silica on the innate resistance of inbred mice to Salmonella typhimurium infection. Infect Immun. 1979 Aug;25(2):513–520. doi: 10.1128/iai.25.2.513-520.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Page D. T., Garvey J. S. Isolation and characterization of hepatocytes and Kupffer cells. J Immunol Methods. 1979;27(2):159–173. doi: 10.1016/0022-1759(79)90262-x. [DOI] [PubMed] [Google Scholar]
  19. Plant J. E., Blackwell J. M., O'Brien A. D., Bradley D. J., Glynn A. A. Are the Lsh and Ity disease resistance genes at one locus on mouse chromosome 1? Nature. 1982 Jun 10;297(5866):510–511. doi: 10.1038/297510a0. [DOI] [PubMed] [Google Scholar]
  20. Sadarangani C., Skamene E., Kongshavn P. A. Cellular basis for genetically determined enhanced resistance of certain mouse strains to listeriosis. Infect Immun. 1980 May;28(2):381–386. doi: 10.1128/iai.28.2.381-386.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. VOLKMAN A., GOWANS J. L. THE ORIGIN OF MACROPHAGES FROM BONE MARROW IN THE RAT. Br J Exp Pathol. 1965 Feb;46:62–70. [PMC free article] [PubMed] [Google Scholar]
  22. Volkman A., Collins F. M. Recovery of delayed-type hypersensitivity in mice following suppressive doses of X-radiation. J Immunol. 1968 Nov;101(5):846–859. [PubMed] [Google Scholar]
  23. van Furth R., Cohn Z. A. The origin and kinetics of mononuclear phagocytes. J Exp Med. 1968 Sep 1;128(3):415–435. doi: 10.1084/jem.128.3.415. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES