African trypanosome infections in mice that lack the interferon-gamma receptor gene: nitric oxide-dependent and -independent suppression of T-cell proliferative responses and the development of anaemia.
Infection of mice with African trypanosomes leads to a severe immunosuppression, mediated by suppressor macrophages. Using ex vivo macrophage culture and in vivo cell transfer, it has been shown that nitric oxide (NO) is a potent effector product of these cells and causes both lymphocyte unresponsiveness and dyserythropoiesis. We explored the role of NO in vivo during trypanosome infection using mice with a disrupted interferon-gamma-receptor gene, which were unable to respond with macrophage activation and NO synthesis. These mice were less effective at controlling parasitaemia than the wild types, but showed an improved splenic T-cell responsiveness and reduced anaemia during the early stages of infection. The data indicate that, in the mouse, NO is a significant mediator of immunosuppression only in early infection. Beyond day 10 of infection, NO-independent mechanisms are of primary significance and the control of parasitaemia and T-cell responsiveness are not directly related.
Mabbott
N A
NA
*Department of Zoology, University of Aberdeen, Aberdeen, UK.
Coulson
P S
PS
Smythies
L E
LE
Wilson
R A
RA
Sternberg
J M
JM
D000740:Anemia / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007371:Interferon-gamma; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D017471:Receptors, Interferon; D003208:Concanavalin A; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase