Gentil group

Overview

About 200 million people suffer from chronic infection with the helminths Brugia malayi and Onchocerca volvulus. Infections by these helminths cause Lymphatic Filariasis and River Blindness, respectively. During the chronic infection, Th2 type immune responses are strongly upregulated as marked by increased IL-5 and eosinophil numbers in the blood. Nonetheless, these cause comparatively little pathology. In contrast, severe disease is associated with Th1 immune responses as characterized by IFNγ production and neutrophil migration. Th1 immune responses are not caused by the filarial parasite itself, but by its endosymbiont Wolbachia. These are released upon natural death of filarial worms or after therapy with diethylcarbamazine (standard therapy for Lymphatic Filariasis).

Our group is focusing on the immune responses to filarial worms and Wolbachia as well as the interactions between filarial and Wolbachia.

Mouse Model of River Blindness

The life cycle of Onchocerca volvulus starts with the blood meal of an uninfected blackfly on an infected individual. During the blood meal, L1 microfilariae are taken up. The microfilariae undergo several molting steps inside the blackfly reaching the infectious L3 stage. Upon the next blood meal, the blackfly transmits the infectious larvae into an uninfected individual. The larvae undergo two more molting steps before reaching the adult stage. The female adult worms are then starting to produce microfilariae.

This infection cycle has not been possible to reproduce in a mouse model. We therefore use immunization studies where we generate protein extracts from adult worms to immunize mice over the course of several weeks. This initiates the generation of an adaptive immune response as demonstrated by antibody production and specific T cell responses. We then inject filarial extract into mouse corneas and examine the infiltration of the cornea by cells of the immune system: neutrophils, eosinophils, macrophages, T cells.