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Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster

Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is the sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune- versus microbe-induced pathology and whether these may differ...

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Autores principales: Vincent, Crystal M., Dionne, Marc S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364183/
https://www.ncbi.nlm.nih.gov/pubmed/34341118
http://dx.doi.org/10.1073/pnas.2026554118
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author Vincent, Crystal M.
Dionne, Marc S.
author_facet Vincent, Crystal M.
Dionne, Marc S.
author_sort Vincent, Crystal M.
collection PubMed
description Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is the sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune- versus microbe-induced pathology and whether these may differ for the sexes. Here, by measuring metabolic and physiological outputs in Drosophila melanogaster with wild-type and mutant immune responses, we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of PGRP-LB, a negative regulator of the immune deficiency (IMD) pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of PGRP-LB, females are more resistant to infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.
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spelling pubmed-83641832021-08-24 Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster Vincent, Crystal M. Dionne, Marc S. Proc Natl Acad Sci U S A Biological Sciences Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is the sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune- versus microbe-induced pathology and whether these may differ for the sexes. Here, by measuring metabolic and physiological outputs in Drosophila melanogaster with wild-type and mutant immune responses, we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of PGRP-LB, a negative regulator of the immune deficiency (IMD) pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of PGRP-LB, females are more resistant to infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost. National Academy of Sciences 2021-08-10 2021-08-02 /pmc/articles/PMC8364183/ /pubmed/34341118 http://dx.doi.org/10.1073/pnas.2026554118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Vincent, Crystal M.
Dionne, Marc S.
Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster
title Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster
title_full Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster
title_fullStr Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster
title_full_unstemmed Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster
title_short Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster
title_sort disparate regulation of imd signaling drives sex differences in infection pathology in drosophila melanogaster
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364183/
https://www.ncbi.nlm.nih.gov/pubmed/34341118
http://dx.doi.org/10.1073/pnas.2026554118
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