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

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 prevent, signal, control or repair damage during infection contribute to the phenotype of disease tolerance. We established enteric infections with the bacterial pathogen in transgenic lines of fruit flies affecting (a major component of the peritrophic matrix), (a cytokine-like molecule), (a negative regulator of reactive oxygen species) and (epithelial growth factor receptor). Flies lacking experienced the highest mortality, while loss of function of either or reduced tolerance in both sexes. The disruption of resulted in a severe loss in tolerance in male flies but had no substantial effect on the ability of female flies to tolerate 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.