DOWN-REGULATION OF MACROPHAGE ACTIVATION IN BRUGIA PAHANGI-INFECTED JIRDS (MERIONES-UNGUICULATUS)

The macrophage is a major component of the inflammatory response induc ed by lymphatic tissue-dwelling filariae. Intraperitoneal (i.p.) infec tions with Brugia pahangi in Mongolian gerbils, or jirds (Meriones ung uiculatus), induce a peritoneal inflammatory response characterized by accumulation of numerous macrophages and fewer eosinophils. This infl ammatory response is associated with the release of microfilariae by f emale worms. The aim of this study was to investigate the activation s tate of the peritoneal macrophages during the course of i.p. infection s with either male or female worms. Activation was determined by a tox oplasmacidal assay and assays which measured the production of tumor n ecrosis factor (TNF) like activity and nitric oxide (NO) production. T he development of these assays with jirds was initially conducted in p arallel with the mouse system, which served as a positive control. Jir d macrophages became activated to kill Toxoplasma gondii by in vivo im munization with Mycobacterium bovis BCG in a pattern similar to that o f mouse macrophages. However, unlike the mouse system, supernatants fr om purified protein derivative-or concanavalin A-stimulated jird splen ocytes plus lipopolysaccharide failed to activate jird macrophages in vitro or induce NO production. These results indicate that factors inv olved in jird macrophage activation may differ from those demonstrated in the mouse system and other systems. i.p. infections of 15 days in duration with either male or female worms induced macrophage activatio n as measured by Toxoplasma killing and TNF production. These response s decreased as the infection progressed to the chronic period on a tim e course that parallels the down regulation of experimental B. pahangi granulomas. There was no evidence of NO production by activated jird macrophages. These data indicate that macrophage function is down modu lated during filarial infection and suggest that mechanisms involved i n macrophage deactivation are related to those that induce down modula tion of the systemic granulomatous inflammatory response in the jird. This response is not dependent on the microfilarial stage of the paras ite and is also independent of mechanisms which induce peritoneal accu mulations of macrophages.