Experimental visceral leishmaniasis: role of endogenous IFN-gamma in host defense and tissue granulomatous response.
The capacity of BALB/c mice to acquire resistance to and eliminate intracellular visceral Leishmania donovani is T cell dependent, associated with a granulomatous tissue reaction, and correlates with the ability to secrete the macrophage-activating lymphokine, IFN-gamma. These responses appear by 4 wk after infection and are fully established by 8 wk. To examine the role of endogenous IFN-gamma, BALB/c mice were injected with anti-IFN-gamma mAb before and for 8 wk after infection. At 4 wk, mAb treatment inhibited the acquisition of resistance to L. donovani and abolished mature granuloma formation. Although liver parasite burdens in mAb-treated mice were fivefold higher than in controls at 8 wk, continually treated mice nevertheless began for form tissue granulomas and decreased their parasite loads by 50% from peak values. The levels of anti-IFN-gamma antibody in the serum of mice injected for 8 wk were appreciably reduced, thus raising the possibilities of either insufficient neutralization of endogenous IFN-gamma at this time point or a pathway independent of IFN-gamma. Although the role of IFN-gamma and the potential effect of an IFN-gamma-independent mechanism in the resolution of visceral infection remain to be defined, these results indicate that IFN-gamma plays a critical role in the early immune response that both optimally controls L. donovani infection and induces the tissue granuloma.
Squires
K E
KE
Division of Infectious Diseases, Cornell University Medical College, New York 10021.
Schreiber
R D
RD
McElrath
M J
MJ
Rubin
B Y
BY
Anderson
S L
SL
Murray
H W
HW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood; D000913:Antibodies, Protozoan / Q000008:administration & dosage / Q000097:blood; D006224:Cricetinae; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D007371:Interferon-gamma