Title | Interferon-gamma and nitric oxide in combination with antibodies are key protective host immune factors during trypanosoma congolense Tc13 Infections. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Magez, S., M. Radwanska, M. Drennan, L. Fick, T. Nath Baral, F. Brombacher, and P. De Baetselier |
Journal | J Infect Dis |
Volume | 193 |
Issue | 11 |
Pagination | 1575-83 |
Date Published | 2006 Jun 1 |
ISSN | 0022-1899 |
Keywords | Animals, Antibodies, Protozoan, B-Lymphocytes, Disease Models, Animal, Female, Immunoglobulin G, Immunoglobulin M, Interferon-gamma, Mice, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide, Parasitemia, Splenectomy, Survival Analysis, Trypanosoma congolense, Trypanosomiasis, African |
Abstract | 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. |
DOI | 10.1086/503808 |
Alternate Journal | J. Infect. Dis. |
PubMed ID | 16652287 |
Grant List | 056708/Z/99 / / Wellcome Trust / United Kingdom |
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