Interferon-gamma and nitric oxide in combination with antibodies are key protective host immune factors during trypanosoma congolense Tc13 Infections.

TitleInterferon-gamma and nitric oxide in combination with antibodies are key protective host immune factors during trypanosoma congolense Tc13 Infections.
Publication TypeJournal Article
Year of Publication2006
AuthorsMagez, S., M. Radwanska, M. Drennan, L. Fick, T. Nath Baral, F. Brombacher, and P. De Baetselier
JournalJ Infect Dis
Volume193
Issue11
Pagination1575-83
Date Published2006 Jun 1
ISSN0022-1899
KeywordsAnimals, 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.

DOI10.1086/503808
Alternate JournalJ. Infect. Dis.
PubMed ID16652287
Grant List056708/Z/99 / / Wellcome Trust / United Kingdom