Fruit fly innate immunity, infection and disease
Infection is a complicated battle for survival between the microbe and the host, but most of what we know about Drosophila innate immunity comes from studies of benign infections by Escherichia coli or Micrococcus luteus; these microbes are effectively killed by the fly in a matter of hours and cause no pathology. The aim of this thesis dissertation was to broaden our understanding of the fly's response to infection by studying the fly's interactions with two microbes it does not clear: (1) the Gram-negative bacteria Salmonella typhimurium and (2) the protozoan parasite Plasmodium gallinaceum . (Part I) By studying S. typhimurium infection in the fly, we discovered an unexpected disconnect between bacterial load and virulence in the fly. This led us to hypothesize that pathogenesis and death by infection in flies is often due as much to the host's response as it is the direct result of microbial action. We then identified fly eiger/TNF as a component of this harmful host response. (Part II) We studied the fly's interactions with Plasmodium by performing a forward genetic screen to identify insect genes affecting Plasmodium infection. We identified 18 mutant fly lines that were resistant to Plasmodium infection. Most of the mutant fly lines were not resistant to bacterial infection, suggesting the genes affected in these lines may specifically be involved in resistance to protozoan parasites. We demonstrated that three out of four mosquito homologs of fly genes identified in the genetic screen affected Plasmodium berghei infection of Anopheles gambiae mosquitoes. This work legitimized the use of Drosophila as a model malarial host and identified interesting genes that can be studied further in the mosquito.