TY - JOUR
T1 - Mechanisms of damage prevention, signalling, and repair impact disease tolerance
AU - Prakash, Arun
AU - Monteith, Katy
AU - Vale, Pedro
N1 - Funding Information:
We acknowledge funding and support to P.F.V. from Branco Weiss fellowship and Chancellor's Fellowship; A.P. was supported by the Darwin Trust PhD studentship. We thank the School of Biological Sciences, University of Edinburgh
Funding Information:
We acknowledge funding and support to P.F.V. from Branco Weiss fellowship and Chancellor's Fellowship; A.P. was supported by the Darwin Trust PhD studentship. We thank the School of Biological Sciences, University of Edinburgh. Acknowledgements
Publisher Copyright:
© 2022 The Authors.
PY - 2022/8/31
Y1 - 2022/8/31
N2 - 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.
AB - 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.
KW - disease tolerance
KW - gut-epithelial immunity
KW - tissue damage repair
KW - oral bacterial infection
KW - enteric infection
KW - infection dose
UR - https://doi.org/10.5281/zenodo.6510215
U2 - 10.1098/rspb.2022.0837
DO - 10.1098/rspb.2022.0837
M3 - Article
SN - 0962-8452
VL - 289
JO - Proceedings of the Royal Society B-Biological Sciences
JF - Proceedings of the Royal Society B-Biological Sciences
IS - 1981
M1 - 20220837
ER -