Research Article: Dietary Cholesterol Modulates Pathogen Blocking by Wolbachia

Date Published: June 27, 2013

Publisher: Public Library of Science

Author(s): Eric P. Caragata, Edwige Rancès, Lauren M. Hedges, Alexander W. Gofton, Karyn N. Johnson, Scott L. O’Neill, Elizabeth A. McGraw, Kenneth D. Vernick.


The bacterial endosymbiont Wolbachia pipientis protects its hosts from a range of pathogens by limiting their ability to form infections inside the insect. This “pathogen blocking” could be explained by innate immune priming by the symbiont, competition for host-derived resources between pathogens and Wolbachia, or the direct modification of the cell or cellular environment by Wolbachia. Recent comparative work in Drosophila and the mosquito Aedes aegypti has shown that an immune response is not required for pathogen blocking, implying that there must be an additional component to the mechanism. Here we have examined the involvement of cholesterol in pathogen blocking using a system of dietary manipulation in Drosophila melanogaster in combination with challenge by Drosophila C virus (DCV), a common fly pathogen. We observed that flies reared on cholesterol-enriched diets infected with the Wolbachia strains wMelPop and wMelCS exhibited reduced pathogen blocking, with viral-induced mortality occurring 2–5 days earlier than flies reared on Standard diet. This shift toward greater virulence in the presence of cholesterol also corresponded to higher viral copy numbers in the host. Interestingly, an increase in dietary cholesterol did not have an effect on Wolbachia density except in one case, but this did not directly affect the strength of pathogen blocking. Our results indicate that host cholesterol levels are involved with the ability of Wolbachia-infected flies to resist DCV infections, suggesting that cholesterol contributes to the underlying mechanism of pathogen blocking.

Partial Text

Wolbachia are maternally inherited bacterial endosymbionts that naturally infect an estimated 40% of all arthropod species [1]. They are primarily known for their manipulation of host reproductive biology, particularly through the phenotype of cytoplasmic incompatibility (CI), which facilitates the spread of the symbiont through wild populations [2]. Some Wolbachia strains manipulate their hosts in other interesting and useful ways, such as through the phenotype known as pathogen blocking, which limits the ability of many pathogenic viruses, bacteria and nematodes to grow in the host [3],[4],[5],[6],[7],[8],[9]. The phenotype has been well characterised in Drosophila fruit flies where it was originally discovered. Blocking occurs against many species of naturally pathogenic viruses including Drosophila C virus and Flock House virus [5],[8],[10],[11]. The effect typically involves a delay in virus-induced mortality for Wolbachia-infected flies, with the strength of the effect varying by strain and pathogen type [8],[10]. For some strains this is also accompanied by a delay in virus accumulation, although this is not required to delay mortality [10]. Stronger blocking occurs in strains that grow to high density, with lower density strains having little effect [10]. Together these factors imply that Wolbachia can cause interference with pathogen replication.




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