INNATE CONTROL OF THE EARLY COURSE OF INFECTION IN MICE INOCULATED WITH TRYPANOSOMA-MUSCULI

Infections of mice with Trypanosoma musculi result in marked suppressi on of acquired humoral immunity but rapid activation of splenic NK cel l cytotoxicity, We show that both NK cells and activated peritoneal sp ace (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 paralle led by a rising number of NK cells, The decline in cytotoxicity occurs even though the number of splenic Mt cells continues to rise. The cri tical role of NK cells in the control of the early course of T. muscul i infection was demonstrated by the effects of either depleting NK cel ls (antiasialo GM1 treatment) or maintaining them in an activated stat e (poly(I:C) injections), The importance of RIP in controlling the inf ection was suggested by studies involving proteose peptone elicited MP both in vivo and in culture, The results presented here strongly sugg est that innate immunity involving NK cells and MP can control, but no t cure, T. musculi infections. Whether this early innate response infl uences the subsequent acquired, curative response remains to be studie d, Detailed analyses of innate immunity in this experimental infection should suggest new approaches to intervention in early pathogenic inf ections. (C) 1997 Academic Press.