Wolbachia are maternally transmitted endosymbionts that infect a large proportion of arthropods and reduce vector competency of mosquitoes carrying deadly diseases such as Dengue, Zika, West Nile Virus, and Chikungunya. Wolbachia preferentially infect specific host cells, a phenomenon termed tissue tropism. Wolbachia tissue tropism has consequences in proper vertical and horizontal transmission. Although Wolbachia tropism to multiple Drosophila gonadal cell types has been identified, the mechanisms of tropism during development have not been characterized, in part because Wolbachia infected cell types are challenging to study during morphogenesis. Here we describe a novel Wolbachia tropism to polar cells (PCs) of the Drosophila ovary, a developmentally well characterized system. We show that Wolbachia intracellular accumulation is triggered by specific events of PC morphogenesis including differentiation from progenitors, and during stage 8 to 9 transition. Using genetic tools, we also demonstrate that induction of ectopic PC fate is sufficient to drive Wolbachia tropism. These findings implicate a tight coordination of host developmental events with Wolbachia tropism.
Wolbachia tropism to multiple host cell types suggest that host pathways common to these would be conducive to intracellular Wolbachia growth. Indeed, we found that Wnt signaling, is active in gonadal cell types with Wolbachia tropism. Wnt signaling, first characterized in embryonic development and patterning, has novel functions in immunity and intracellular pathogen survival. Using RNAi mediated gene knockdowns, we studied the effect of Wnt signaling on Wolbachia in various infected cell types, including the testis stem cell niche, PCs and germline. Reduction of Wnt signaling caused a decrease in Wolbachia density and increased signaling led to higher density suggesting the reliance of Wolbachia on host Wnt signaling for its tropism. Moreover, expression of ectopic Wnt signaling was sufficient to drive Wolbachia tropism to previously uninfected tissues such as the D. melanogaster female germline stem cell niche. Finally, small molecule Wnt signaling agonists were sufficient to drive high Wolbachia titers in mosquito cell lines. These findings describe the effect of host signaling on Wolbachia tropism and provide an approach to affect Wolbachia levels in disease-causing vectors, thereby contributing to Wolbachia based vector control strategies.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/33092 |
| Date | 13 November 2018 |
| Creators | Kamath, Ajit |
| Contributors | Frydman, Horacio |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution 4.0 International, http://creativecommons.org/licenses/by/4.0/ |
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