Negative immune regulation contributes to disease tolerance in Drosophila. Prakash, A., Monteith, K. M., & Vale, P. F. May, 2023. Pages: 2021.09.23.461574 Section: New Results
Negative immune regulation contributes to disease tolerance in Drosophila [link]Paper  doi  abstract   bibtex   10 downloads  
Disease tolerance is an infection phenotype where hosts show relatively high health despite harbouring elevated pathogen loads. Variation in the ability to reduce immunopathology may explain why some hosts can tolerate higher pathogen burdens with reduced pathology. Negative immune regulation would therefore appear to be a clear candidate for a mechanism underlying disease tolerance. Here, we examined how the negative regulation of the immune deficiency (IMD) pathway affects disease tolerance in Drosophila melanogaster when infected with four doses of the gram-negative bacterial pathogen Pseudomonas entomophila. We find that while flies unable to regulate the IMD response exhibited higher expression of antimicrobial peptides and lower bacterial loads as expected, this was not accompanied by a proportional reduction in mortality. Instead, UAS-RNAi knockdown of negative regulators of IMD (pirk and caudal) substantially increased the per-pathogen-mortality in both males and females across all tested infectious doses. Our results therefore highlight that in addition to regulating an efficient pathogen clearance response, negative regulators of IMD also contribute to disease tolerance.
@misc{prakash_negative_2023,
	title = {Negative immune regulation contributes to disease tolerance in {Drosophila}},
	copyright = {© 2023, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), CC BY 4.0, as described at http://creativecommons.org/licenses/by/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/2021.09.23.461574v3},
	doi = {10.1101/2021.09.23.461574},
	abstract = {Disease tolerance is an infection phenotype where hosts show relatively high health despite harbouring elevated pathogen loads. Variation in the ability to reduce immunopathology may explain why some hosts can tolerate higher pathogen burdens with reduced pathology. Negative immune regulation would therefore appear to be a clear candidate for a mechanism underlying disease tolerance. Here, we examined how the negative regulation of the immune deficiency (IMD) pathway affects disease tolerance in Drosophila melanogaster when infected with four doses of the gram-negative bacterial pathogen Pseudomonas entomophila. We find that while flies unable to regulate the IMD response exhibited higher expression of antimicrobial peptides and lower bacterial loads as expected, this was not accompanied by a proportional reduction in mortality. Instead, UAS-RNAi knockdown of negative regulators of IMD (pirk and caudal) substantially increased the per-pathogen-mortality in both males and females across all tested infectious doses. Our results therefore highlight that in addition to regulating an efficient pathogen clearance response, negative regulators of IMD also contribute to disease tolerance.},
	language = {en},
	urldate = {2024-06-04},
	publisher = {bioRxiv},
	author = {Prakash, Arun and Monteith, Katy M. and Vale, Pedro F.},
	month = may,
	year = {2023},
	note = {Pages: 2021.09.23.461574
Section: New Results},
}

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