Host-pathogen interactions in filarial worm infections

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Wolbachia are common intracellular bacteria found in arthropods and filarial nematodes. The association between filarial worms and their mutualistic and obligatory endosymbionts is different from that of Wolbachia with insects: in worms they appear to provide crucial elements for fitness and survival, whereas the insects are mostly viable without Wolbachia. This project evaluates how Wolbachia impact the regulation of host genes, how they obtain essential metabolites for their survival, and how they evade the hosts intracellular immune defenses. In this project we are evaluating how Wolbachia change the transcriptional profile of the host cells they infect. We have identified miRNAs that are differentially regulated in response to Wolbachia disruption in B. malayi worms, and we are testing miRNAs identified as differentially expressed in mosquito cell lines with or without Wolbachia. We aim to characterize host genes that are regulated by Wolbachia via miRNA manipulation. We are also looking at the induction of cellular autophagy which was shown to drastically decrease the number of bacteria in worms, and to block embryogenesis and the release of microfilariae (Mf) by treated female worms. We have identified chemical compounds that induce autophagy in nematodes, and plan to test their ability to eliminate Wolbachia in adult worms. The results from our research could help direct future investigations into a defined set of B. malayi genes that are important for maintaining the Wolbachia-filarial worm mutualistic co-dependencies, and aid in the search for novel macrofilaricidal drugs that affect symbiosis.