Innate control of the early course of infection in mice inoculated with Trypanosoma musculi.

Infections of mice with Trypanosoma musculi result in marked suppression of acquired humoral immunity but rapid activation of splenic NK cell cytotoxicity. We show that both NK cells and activated peritoneal space (PS) macrophages (MP) participate in the innate immune control of T. musculi infections preceding escape of curative antibody production from suppression. Splenic NK cytotoxicity reaches a peak on Days 3-4 of infection and then rapidly declines. Rising cytotoxicity is paralleled by a rising number of NK cells. The decline in cytotoxicity occurs even though the number of splenic NK cells continues to rise. The critical role of NK cells in the control of the early course of T. musculi infection was demonstrated by the effects of either depleting NK cells (antiasialo GM1 treatment) or maintaining them in an activated state (poly(I:C) injections). The importance of MP in controlling the infection was suggested by studies involving proteose peptone elicited MP both in vivo and in culture. The results presented here strongly suggest that innate immunity involving NK cells and MP can control, but not cure, T. musculi infections. Whether this early innate response influences the subsequent acquired, curative response remains to be studied. Detailed analyses of innate immunity in this experimental infection should suggest new approaches to intervention in early pathogenic infections.