Stage-Specific Induction of Cytokines Regulates the Immune Response in Lymphatic Filariasis

Abstract

Parasite stage-specific T cell responses were studied in Indians with lymphatic filariasis manifesting as elephantiasis (CP,n= 11) and asymptomatic microfilaremia (MF,n= 8), using antigens derived from the microfilarial, adult male only, and mixed adult male and female worms. Proliferative responses to microfilarial and mixed (male–female adult worm) antigens in MF individuals were markedly impaired compared to corresponding responses in individuals with CP. In contrast, T cell proliferative responses to adult male-derived antigens were not statistically different between the two groups. Analysis of antigen-driven cytokine secretion by peripheral blood mononuclear cells from MF and CP individuals revealed significantly lower IL-2 and IFN-γ production by MF in response to microfilarial and mixed antigens (but not to adult male antigen) compared to CP individuals. No differences were observed between MF and CP in parasite antigen-driven IL-4 or IL-5 production. Spontaneous and parasite-specific IL-10 secretion was also measured to determine if cytokine cross-regulation of Th1 responses may be a mechanism underlying the observed Th1 suppression. Spontaneous and microfilarial antigen-driven IL-10 was found to be significantly higher in MF than in CP individuals. These data indicate that MF individuals exhibit preferentially impaired Th1-type responses to microfilarial antigens and that microfilarial-induced IL-10 may be critical in the downregulation of specific Th1 responses.