Mechanisms of damage prevention, signalling, and repair impact disease tolerance

Arun Prakash, Katy Monteith, Pedro Vale

Research output: Contribution to journalArticlepeer-review

Abstract

The insect gut is frequently exposed to pathogenic threats and must not only clear these potential infections, but also tolerate relatively high microbe loads. In contrast to the mechanisms that eliminate pathogens, we currently know less about the mechanisms of disease tolerance. We investigated how well-described mechanisms that either prevent, signal, control, or repair damage during infection contribute to the phenotype of disease tolerance. We established enteric infections with the bacterial pathogen Pseudomonas entomophila in transgenic lines of Drosophila melanogaster fruit flies affecting dcy (a major component of the peritrophic matrix), upd3 (a cytokine-like molecule), irc (a negative regulator of reactive oxygen species) and egfr1 (epithelial growth factor receptor). Flies lacking dcy experienced the highest mortality, while loss of function of either irc or upd3 reduced tolerance in both sexes. The disruption of egfr1 resulted in a severe loss in tolerance in male flies but had no substantial effect on the ability of female flies to tolerate P. entomophila infection, despite carrying greater microbe loads than males. Together, our findings provide evidence for the role of damage limitation mechanisms in disease tolerance and highlight how sexual dimorphism in these mechanisms could generate sex differences in infection outcomes.
Original languageEnglish
JournalProceedings of the Royal Society B-Biological Sciences
Publication statusAccepted/In press - 1 Aug 2022

Keywords

  • disease tolerance
  • gut-epithelial immunity
  • tissue damage repair
  • oral bacterial infection
  • enteric infection
  • infection dose

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