Dietary cholesterol modulates pathogen blocking by Wolbachia

PLoS Pathog. 2013;9(6):e1003459. doi: 10.1371/journal.ppat.1003459. Epub 2013 Jun 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes* / metabolism
  • Aedes* / microbiology
  • Aedes* / virology
  • Animals
  • Cholesterol / metabolism
  • Cholesterol / pharmacology*
  • Dicistroviridae / metabolism*
  • Dietary Fats / metabolism
  • Dietary Fats / pharmacology*
  • Drosophila melanogaster
  • Host-Pathogen Interactions / drug effects*
  • Host-Pathogen Interactions / physiology
  • Wolbachia / physiology*

Substances

  • Dietary Fats
  • Cholesterol

Grants and funding

This work was supported by a grant to SLO from the Foundation for the National Institute of Health through the Grand Challenges in Global Health Initiative of the Bill and Melinda Gates Foundation, and an ARC Discovery Project grant to KNJ and SLO DP1092492. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.