Innate Resistance to Trypanosoma congolense Infections: Differential Production of Nitric Oxide by Macrophages from Susceptible BALB/c and Resistant C57Bl/6 Mice

• DOI: 10.1006/expr.1999.4408
• Publication Date: 2002-09-17T22:30:52Z
• Authors: Radhey S. Kaushik; Jude E. Uzonna; John R. Gordon; Henry Tabel
• Keywords: Mice, Inbred BALB C; Trypanosoma congolense; Macrophages; Dose-Response Relationship, Immunologic; Antibodies, Monoclonal; Bone Marrow Cells; Nitric Oxide; Immunity, Innate; 3. Good health; Mice, Inbred C57BL; Interferon-gamma; Mice; 03 medical and health sciences; Trypanosomiasis, African; 0302 clinical medicine; Immunoglobulin M; Phagocytosis; Immunoglobulin G; Macrophages, Peritoneal; Animals; Female; Disease Susceptibility; Cells, Cultured

BALB/c and C57B1/6 mice differ in resistance to Trypanosoma congolense infections. Evidence suggests that macrophages play a central role in the resistance to trypanosomiasis. Nitric oxide (NO) produced by macrophages in response to various stimuli or pathogens is one of the important arms of nonspecific immunity. We investigated the production of NO by the peritoneal macrophages and bone marrow-derived macrophages (BMDM) from trypanosome-resistant C57B1/6 and -susceptible BALB/c mice following stimulation with T. congolense whole cell extract (WCE) or following phagocytosis of T. congolense mediated by anti-variant surface glycoprotein (VSG) antibodies of IgM or IgG2a isotype. C57B1/6 peritoneal macrophages as well as BMDM produced significantly more NO than similar BALB/c macrophages in response to T. congolense lysate and IFN-gamma. In both BALB/c and C57B1/6 BMDM cultures, phagocytosis of T. congolense mediated by anti-VSG antibodies of IgG2a isotype in the presence of IFNgamma induced two- to ninefold more NO than phagocytosis mediated by IgM antibodies and C57B1/6 BMDM produced significantly higher amounts of NO than BALB/c BMDM under these conditions. NO produced by BMDM was found to exert trypanostatic effect on T. congolense in vitro, but was not found to influence the in vivo infectivity of these treated parasites under the conditions used in this study.