Interferon-gamma and nitric oxide in combination with antibodies are key protective host immune factors during trypanosoma congolense Tc13 Infections.
The control of chronic Trypanosoma congolense trypanosomiasis was analyzed using several gene-deficient mouse strains. First, interferon (IFN)-gamma receptor (IFN-gamma-R)-deficient mice were used to show that IFN- gamma -mediated immune activation is crucial for parasitemia control. Second, infections in major histocompatibility complex (MHC) class II-deficient mice indicate that this molecule is needed for initiation of IFN- gamma and subsequent tumor necrosis factor (TNF) production. Downstream of IFN-gamma-R signaling, inducible NO synthase (iNOS)-dependent trypanosome killing occurs, as is shown by the hypersusceptible phenotype of iNOS-deficient mice. Besides proinflammatory responses, B cells and, more specifically, immunoglobulin (Ig) G antibodies are crucial for parasite killing. Hence, parasitemia control is abolished in B cell-deficient mice, whereas IgM-deficient mice control the infection as efficiently as do wild-type mice. In addition, splenectomized mice that have a normal IgM response but an impaired IgG2a/3 response fail to control T. congolense infection. Collectively, these results suggest that host protective immunity against T. congolense is critically dependent on the combined action of the proinflammatory mediators/effectors IFN- gamma , TNF, and NO and antiparasite IgGs.
Magez
Stefan
S
Laboratory of Cellular and Molecular Immunology, Department of Molecular and Cellular Recognition, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel, Brussels, Belgium.
Radwanska
Magdalena
M
Drennan
Michael
M
Fick
Lizette
L
Baral
Toya Nath
TN
Brombacher
Frank
F
De Baetselier
Patrick
P
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology*; D018512:Parasitemia / Q000276:immunology; D013156:Splenectomy; D016019:Survival Analysis; D014348:Trypanosoma congolense / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000276:immunology*
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009569:Nitric Oxide; D007371:Interferon-gamma