Brugia pahangi:Differential Induction and Regulation of Jird Inflammatory Responses by Life-Cycle Stages

Abstract

It has been hypothesized that different life-cycle stages of filarial nematodes induce different host responses. This concept was examined in theBrugia pahangi–jird model of lymphatic filariasis by measuring the kinetics of inflammatory responses to parasite antigens following intraperitoneal inoculation of different life-cycle stages. For this purpose, viable female or male worms, L3, L4, or microfilarial stages, were used. Dead worms served as controls. Worm and microfilarial burdens, pulmonary granulomatous inflammation (PGRN) to soluble adult worm antigen (SAWA)-coated beads, and peritoneal eosinophil and macrophage numbers were assessed at different days post-inoculation. All jirds inoculated with any of these life-cycle stages developed an early PGRN to SAWA which was later significantly reduced. Only viable worms induced down-regulation of the PGRN response. These results indicate that the hyporesponsive state is induced and maintained by all life-cycle stages. Also, the degree of granulomatous response was influenced by worm burden, with larger worm burdens inducing lower initial levels of PGRN to SAWA. Peritoneal inflammatory responses differed from the systemic response in that numbers of macrophages increased with time and microfilarial accumulation. No correlation was observed between peritoneal inflammatory responses measured by eosinophil and macrophage numbers and PGRN to SAWA.