Mechanisms of damage prevention, signalling, and repair impact the ability of Drosophila to tolerate enteric bacterial infection

Abstract

AbstractMany insects thrive on decomposing and decaying organic matter containing a large diversity of both commensal and pathogenic microorganisms. The insect gut is therefore frequently exposed to pathogenic threats and must be able not only to detect and clear these potential infections, but also be able to repair the resulting damage to gut tissues in order to tolerate relatively high microbe loads. In contrast to the mechanisms that eliminate pathogens, we currently know less about the mechanisms of disease tolerance, and most of this knowledge stems from systemic infections. Here we investigated how well-described mechanisms that either prevent, signal, control, or repair tissue damage during infection contribute to the phenotype of disease tolerance during gut infection. We orally infected adult Drosophila melanogaster flies with the bacterial pathogen Pseudomonas entomophila in several loss-of-function mutants lacking epithelial responses including damage preventing dcy (drosocrystallin - a major component of the peritrophic matrix), damage signalling upd3 (unpaired protein, a cytokine-like molecule), damage controlling irc (immune-regulated catalase, a negative regulator of reactive oxygen species) and tissue damage repairing egfr1 (epidermal growth factor receptor). Overall, we detect effects of all these mechanisms on disease tolerance. The deterioration of the peritrophic matrix in dcy mutants resulted in the highest loss of tolerance, while loss of function of either irc or upd3 also reduced tolerance in both sexes. The absence of tissue damage repair signalling (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 empirical evidence for the role of damage limitation mechanisms in disease tolerance and highlight how sex differences in these mechanisms could generate sexual dimorphism in immunity.