Innate resistance to Trypanosoma congolense infections: Differential production of nitric oxide by macrophages from susceptible BALB c and resistant C57B1/6 mice

BALB/c and C57B1/6 mice differ in resistance to Trypanosoma congolense infe ctions. Evidence suggests that macrophages play a central role in the resis tance to trypanosomiasis. Nitric oxide (NO) produced by macrophages in resp onse to various stimuli or pathogens is one of the important arms of nonspe cific immunity. We investigated the production of NO by the peritoneal macr ophages and bone marrow-derived macrophages (BMDM) from trypanosome-resista nt C57B1/6 and -susceptible BALB/c mice following stimulation with T. congo lense whole cell extract (WCE) or following phagocytosis of T. congolense m ediated by anti-variant surface glycoprotein (VSG) antibodies of IgM or IgG 2a isotype. C57B1/6 peritoneal macrophages as well as BMDM produced signifi cantly 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, phagocytos is of T. congolense mediated by anti-VSG antibodies of IgG2a isotype in the presence of IFN gamma induced two- to ninefold more NO than phagocytosis m ediated by IgM antibodies and C57B1/6 BMDM produced significantly higher am ounts of NO than BALB/c BMDM under these conditions. NO produced by BMDM wa s found to exert trypanostatic effect on T. congolense in vitro, but was no t found to influence the in vivo infectivity of these treated parasites und er the conditions used in this study. (C) 1999 Academic Press.