Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products.
In the present study, we examined the modulation of MHC class II and class I gene products on BALB/c macrophages infected with the obligate intracellular protozoan Leishmania donovani. Our findings indicated that this organism suppressed macrophage expression of both classes of MHC antigens. These effects varied somewhat, depending on whether cells were in the basal state or were stimulated with interferon-gamma. Thus, class II density on interferon-gamma-treated infected macrophages was suppressed by as much as 90%, relative to lymphokine-stimulated control cells. Induction of H-2K and H-2D by lymphokine treatment of infected macrophages was also markedly reduced. In the basal (non-lymphokine-treated) state, infected cells also showed reduced expression of H-2K and H-2D, but not I-A or I-E. The latter result was related to minimal levels of class II molecules on normal, in vitro cultured macrophages. Suppression of MHC gene products correlated with both the duration and intensity of leishmania infection and could not be overcome by increasing doses of interferon-gamma. Culture of cells under conditions of cyclooxygenase inhibition completely abolished elevated synthesis of prostaglandin E2 by infected macrophages and augmented their responsiveness to lymphokine induction of class II antigens by 60 to 80%. These results indicate that L. donovani is capable of subverting a critical macrophage accessory function required for the induction of T lymphocyte immunity. This mechanism could account, at least in part, for defective parasite-specific cell-mediated immunity seen during infections with this protozoan.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000469:parasitology*; D002478:Cells, Cultured; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007372:Interferons / Q000494:pharmacology; D007700:Kinetics; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D008285:Major Histocompatibility Complex; D008469:Meclofenamic Acid / Q000494:pharmacology; D051379:Mice; D011458:Prostaglandins E / Q000502:physiology
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D011458:Prostaglandins E; D008469:Meclofenamic Acid; D007372:Interferons; D015232:Dinoprostone