Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1981 Jan;102(1):127–132.

Interactions between murine macrophages and obligate intracellular protozoa.

T C Jones
PMCID: PMC1903444  PMID: 7468756

Abstract

The diversity of interactions between obligate intracellular protozoa and murine macrophages is just being elucidated. Protozoa of the genera Toxoplasma, Leishmania, and Trypanosoma all enter and replicate within macrophages. This review describes similarities and differences among these organisms with regard to entry mechanisms, sites of replication in the phagolysosomal system, metabolic requirements, effects on macrophage function, macrophage handling of protozoal antigens, the relationship to genetics of immune response, and the characteristics of lymphokine-induced microbicidal and microbistatic processes. These organisms each enter the macrophage by endocytosis, but they then reside at different sites in relation to the phagolysosomal system. The basis of obligate parasitism remains unknown; however, both the protozoa and the host cell have important effects on the function of the other during parasitism. The macrophage may play a pivotal role in the immunosuppression associated with the early stages of infection by each of these microbes. Genetic influences on the response to infection have been clearly identified in murine models. Lymphocyte products from immune cells have marked effects on the interactions of protozoa and macrophages, under some conditions stimulating protozoacidal mechanisms, and in some protozoastatic responses. The dynamic balance between protozoal parasitism and macrophage response must be further defined in order to determine the potential value of chemotherapeutic or immunologic intervention.

Full text

PDF
127

Selected References

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

  1. Aikawa M., Miller L. H., Johnson J., Rabbege J. Erythrocyte entry by malarial parasites. A moving junction between erythrocyte and parasite. J Cell Biol. 1978 Apr;77(1):72–82. doi: 10.1083/jcb.77.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Akiyama H. J., McQuillen N. K. Interaction and transformation of Leishmania donovani within in vitro cultured cells. An electron microscopical study. Am J Trop Med Hyg. 1972 Nov;21(6):873–879. doi: 10.4269/ajtmh.1972.21.873. [DOI] [PubMed] [Google Scholar]
  3. Bang F. B., Warwick A. MOUSE MACROPHAGES AS HOST CELLS FOR THE MOUSE HEPATITIS VIRUS AND THE GENETIC BASIS OF THEIR SUSCEPTIBILITY. Proc Natl Acad Sci U S A. 1960 Aug;46(8):1065–1075. doi: 10.1073/pnas.46.8.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Behin R., Mauel J., Sordat B. Leishmania tropica: pathogenicity and in vitro macrophage function in strains of inbred mice. Exp Parasitol. 1979 Aug;48(1):81–91. doi: 10.1016/0014-4894(79)90057-2. [DOI] [PubMed] [Google Scholar]
  5. Berens R. L., Deutsch-King L. C., Marr J. J. Leishmania donovani and Leishmania braziliensis: hexokinase, glucose 6-phosphate dehydrogenase, and pentose phosphate shunt activity. Exp Parasitol. 1980 Feb;49(1):1–8. doi: 10.1016/0014-4894(80)90049-1. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Buchmüller Y., Mauel J. Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes. J Exp Med. 1979 Aug 1;150(2):359–370. doi: 10.1084/jem.150.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chang K. P., Dwyer D. M. Leishmania donovani. Hamster macrophage interactions in vitro: cell entry, intracellular survival, and multiplication of amastigotes. J Exp Med. 1978 Feb 1;147(2):515–530. doi: 10.1084/jem.147.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang K. P., Dwyer D. M. Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro. Science. 1976 Aug 20;193(4254):678–680. doi: 10.1126/science.948742. [DOI] [PubMed] [Google Scholar]
  10. Chang K. P. Leishmania donovani: promastigote--macrophage surface interactions in vitro. Exp Parasitol. 1979 Oct;48(2):175–189. doi: 10.1016/0014-4894(79)90097-3. [DOI] [PubMed] [Google Scholar]
  11. Chang K. P. Leishmania infection of human skin fibroblasts in vitro: absence of phagolysosomal fusion after induced phagocytosis of promastigotes, and their intracellular transformation. Am J Trop Med Hyg. 1978 Nov;27(6):1084–1096. doi: 10.4269/ajtmh.1978.27.1084. [DOI] [PubMed] [Google Scholar]
  12. Droller M. J., Remington J. S. Lymphocyte and macrophage adenyl cyclase activity in animals with enhanced cell-mediated resistance to infection and tumors. Cell Immunol. 1975 Oct;19(2):349–355. doi: 10.1016/0008-8749(75)90216-6. [DOI] [PubMed] [Google Scholar]
  13. Dvorak J. A., Howe C. L. Toxoplasma gondii-vertebrate cell interactions. II. The intracellular reproductive phase. J Protozool. 1979 Feb;26(1):114–117. doi: 10.1111/j.1550-7408.1979.tb02742.x. [DOI] [PubMed] [Google Scholar]
  14. Dzbeński T. H., Zielińska E. Antibody-induced formation of caps in Toxoplasma gondii. Experientia. 1976 Apr 15;32(4):454–456. doi: 10.1007/BF01920792. [DOI] [PubMed] [Google Scholar]
  15. Edelson P. J., Cohn Z. A. Effects of concanavalin A on mouse peritoneal macrophages. I. Stimulation of endocytic activity and inhibition of phago-lysosome formation. J Exp Med. 1974 Nov 1;140(5):1364–1386. doi: 10.1084/jem.140.5.1364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. El-On J., Schnur L. F., Greenblatt C. L. Leishmania donovani: physicochemical, immunological, and biological characterization of excreted factor from promastigotes. Exp Parasitol. 1979 Apr;47(2):254–269. doi: 10.1016/0014-4894(79)90078-x. [DOI] [PubMed] [Google Scholar]
  17. Goodwin L. G., Green D. G., Guy M. W., Voller A. Immunosuppression during trypanosomiasis. Br J Exp Pathol. 1972 Feb;53(1):40–43. [PMC free article] [PubMed] [Google Scholar]
  18. Greenwood B. M., Playfair J. H., Torrigiani G. Immunosuppression in murine malaria. I. General characteristics. Clin Exp Immunol. 1971 Mar;8(3):467–478. [PMC free article] [PubMed] [Google Scholar]
  19. Handman E., Ceredig R., Mitchell G. F. Murine cutaneous leishmaniasis: disease patterns in intact and nude mice of various genotypes and examination of some differences between normal and infected macrophages. Aust J Exp Biol Med Sci. 1979 Feb;57(1):9–29. doi: 10.1038/icb.1979.2. [DOI] [PubMed] [Google Scholar]
  20. Handman E., Greenblatt C. L. Promotion of leishmanial infections in non-permissive host macrophages by conditioned medium. Z Parasitenkd. 1977 Sep 21;53(2):143–147. doi: 10.1007/BF00380458. [DOI] [PubMed] [Google Scholar]
  21. Handman E., Spira D. T. Growth of Leishmania amastigotes in macrophages from normal and immune mice. Z Parasitenkd. 1977 Aug 25;53(1):75–81. doi: 10.1007/BF00383117. [DOI] [PubMed] [Google Scholar]
  22. Hart P. D., Young M. R. Interference with normal phagosome-lysosome fusion in macrophages, using ingested yeast cells and suramin. Nature. 1975 Jul 3;256(5512):47–49. doi: 10.1038/256047a0. [DOI] [PubMed] [Google Scholar]
  23. Huldt G., Gard S., Olovson S. G. Effect of Toxoplasma gondii on the thymus. Nature. 1973 Aug 3;244(5414):301–303. doi: 10.1038/244301a0. [DOI] [PubMed] [Google Scholar]
  24. Jones T. C., Hirsch J. G. The interaction between Toxoplasma gondii and mammalian cells. II. The absence of lysosomal fusion with phagocytic vacuoles containing living parasites. J Exp Med. 1972 Nov 1;136(5):1173–1194. doi: 10.1084/jem.136.5.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jones T. C., Len L., Hirsch J. G. Assessment in vitro of immunity against Toxoplasma gondii. J Exp Med. 1975 Feb 1;141(2):466–482. doi: 10.1084/jem.141.2.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jones T. C., Len L. Pinocytic rates of macrophages from mice immunized against Toxoplasma gondii and macrophages stimulated to inhibit toxoplasma in vitro. Infect Immun. 1976 Oct;14(4):1011–1013. doi: 10.1128/iai.14.4.1011-1013.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Jones T. C., Masur H., Len L., Fu T. L. Lymphocyte-macrophage interaction during control of intracellular parasitism. Am J Trop Med Hyg. 1977 Nov;26(6 Pt 2):187–193. doi: 10.4269/ajtmh.1977.26.187. [DOI] [PubMed] [Google Scholar]
  28. Jones T. C., Yeh S., Hirsch J. G. The interaction between Toxoplasma gondii and mammalian cells. I. Mechanism of entry and intracellular fate of the parasite. J Exp Med. 1972 Nov 1;136(5):1157–1172. doi: 10.1084/jem.136.5.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Keithly J. S. Infectivity of Leishmania donovani amastigotes and promastigotes for golden hamsters. J Protozool. 1976 May;23(2):244–245. doi: 10.1111/j.1550-7408.1976.tb03763.x. [DOI] [PubMed] [Google Scholar]
  30. Marr J. J., Berens R. L. Antileishmanial effect of allopurinol. II. Relationship of adenine metabolism in Leishmania species to the action of allopurinol. J Infect Dis. 1977 Dec;136(6):724–732. doi: 10.1093/infdis/136.6.724. [DOI] [PubMed] [Google Scholar]
  31. Mauel J., Buchmüller Y., Behin R. Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes. J Exp Med. 1978 Aug 1;148(2):393–407. doi: 10.1084/jem.148.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mogensen S. C. Genetics of macrophage-controlled resistance to hepatitis induced by herpes simplex virus type 2 in mice. Infect Immun. 1977 Aug;17(2):268–273. doi: 10.1128/iai.17.2.268-273.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mogensen S. C. Role of macrophages in natural resistance to virus infections. Microbiol Rev. 1979 Mar;43(1):1–26. doi: 10.1128/mr.43.1.1-26.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Murray H. W., Cohn Z. A. Macrophage oxygen-dependent antimicrobial activity. I. Susceptibility of Toxoplasma gondii to oxygen intermediates. J Exp Med. 1979 Oct 1;150(4):938–949. doi: 10.1084/jem.150.4.938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Murray H. W., Juangbhanich C. W., Nathan C. F., Cohn Z. A. Macrophage oxygen-dependent antimicrobial activity. II. The role of oxygen intermediates. J Exp Med. 1979 Oct 1;150(4):950–964. doi: 10.1084/jem.150.4.950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nathan C., Nogueira N., Juangbhanich C., Ellis J., Cohn Z. Activation of macrophages in vivo and in vitro. Correlation between hydrogen peroxide release and killing of Trypanosoma cruzi. J Exp Med. 1979 May 1;149(5):1056–1068. doi: 10.1084/jem.149.5.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nogueira N., Cohn Z. Trypanosoma cruzi: mechanism of entry and intracellular fate in mammalian cells. J Exp Med. 1976 Jun 1;143(6):1402–1420. doi: 10.1084/jem.143.6.1402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Nogueira N., Gordon S., Cohn Z. Trypanosoma cruzi: the immunological induction of macrophage plasminogen activator requires thymus-derived lymphocytes. J Exp Med. 1977 Jul 1;146(1):172–183. doi: 10.1084/jem.146.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pfefferkorn E. R., Pfefferkorn L. C. Quantitative studies of the mutagenesis of Toxoplasma gondii. J Parasitol. 1979 Jun;65(3):364–370. [PubMed] [Google Scholar]
  40. Pfefferkorn E. R., Pfefferkorn L. C. Specific labeling of intracellular Toxoplasma gondii with uracil. J Protozool. 1977 Aug;24(3):449–453. doi: 10.1111/j.1550-7408.1977.tb04774.x. [DOI] [PubMed] [Google Scholar]
  41. Pfefferkorn E. R., Pfefferkorn L. C. Toxoplasma gondii: isolation and preliminary characterization of temperature-sensitive mutants. Exp Parasitol. 1976 Jun;39(3):365–376. doi: 10.1016/0014-4894(76)90040-0. [DOI] [PubMed] [Google Scholar]
  42. Preston P. M., Behbehani K., Dumonde D. C. Experimental cutaneous leishmaniasis: VI: anergy and allergy in the cellular immune response during non-healing infection in different strains of mice. J Clin Lab Immunol. 1978 Nov;1(3):207–219. [PubMed] [Google Scholar]
  43. Reed S. G., Larson C. L., Speer C. A. Suppression of cell-mediated immunity in experimental Chagas' disease. Z Parasitenkd. 1977 Jun 3;52(1):11–17. doi: 10.1007/BF00380553. [DOI] [PubMed] [Google Scholar]
  44. Remington J. S., Krahenbuhl J. L., Mendenhall J. W. A role for activated macrophages in resistance to infection with Toxoplasma. Infect Immun. 1972 Nov;6(5):829–834. doi: 10.1128/iai.6.5.829-834.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sherman I. W. Biochemistry of Plasmodium (malarial parasites). Microbiol Rev. 1979 Dec;43(4):453–495. doi: 10.1128/mr.43.4.453-495.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Silverstein S. Macrophages and viral immunity. Semin Hematol. 1970 Apr;7(2):185–214. [PubMed] [Google Scholar]
  47. Slutzky G. M., El-On J., Greenblatt C. L. Leishmanial excreted factor: protein-bound and free forms from promastigote cultures of Leishmania tropica and Leishmania donovani. Infect Immun. 1979 Dec;26(3):916–924. doi: 10.1128/iai.26.3.916-924.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Strickland G. T., Sayles P. C. Depressed antibody responses to a thymus-dependent antigen in toxoplasmosis. Infect Immun. 1977 Jan;15(1):184–190. doi: 10.1128/iai.15.1.184-190.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Weiser W., Bang F. B. Macrophages genetically resistant to mouse hepatitis virus converted in vitro to susceptible macrophages. J Exp Med. 1976 Mar 1;143(3):690–695. doi: 10.1084/jem.143.3.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wilson C. B., Tsai V., Remington J. S. Failure to trigger the oxidative metabolic burst by normal macrophages: possible mechanism for survival of intracellular pathogens. J Exp Med. 1980 Feb 1;151(2):328–346. doi: 10.1084/jem.151.2.328. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES