Wolbachia endosymbiont of Brugia malayi elicits Th-17 mediated proinflammatory immune response through surface protein (WSP)

Abstract

Wolbachia is an endosymbiotic bacterium of filarial nematode Brugia malayi. The symbiotic relationship between Wolbachia and its filarial host is dependent on some interactions between the proteins of both organisms. However, very little is known about Wolbachia proteins that are involved in inflammatory pathology of the host during lymphatic filariasis. In the present study, we cloned, expressed and purified Wolbachia surface protein (r-wsp) from Wolbachia and administered it into mice, either alone or in combination with infective larvae of B. malayi (Bm-L3) and monitored the developing immune response in infected animals. Our results show that spleens and mesenteric lymph nodes (mLNs) of mice immunized with either r-wsp or infected with Bm-L3 show increased percentages of CD4+ Th17 cells and Th1 cytokines like IFN-γ and IL-2 along with decreased percentages of Tregs, Th2 cytokines like IL-4 and IL-10 and Transforming growth factor beta (TGF-β) levels in culture supernatants of splenocytes. These observations were more prominent in mice immunized with r-wsp alone. Interestingly, when mice were first immunized with r-wsp and subsequently infected with Bm-L3, percentages of CD4+ Th17 cells and Th1 cytokines increased even further while that of Tregs, Th2 cytokines and TGF-β levels decreased. These results for the first time show that r-wsp acts synergistically with Bm-L3 in promoting pro-inflammatory response by increasing Th17 cells and at the same time diminishes host immunological tolerance by decreasing Tregs cells and TGF-β secretion.