Skeletal muscle fibers play a functional role in host defense during sepsis in mice

Abstract Skeletal muscles secrete a wide variety of immunologically active cytokines, but the functional significance of this response to in vivo innate immunity is not understood. We addressed this by knocking out the toll receptor adapter protein, Myd88, only in skeletal muscle fibers (skmMyd88KO)...

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Autores principales:	Orlando Laitano, Gerard P. Robinson, Kevin O. Murray, Christian K. Garcia, Alex J. Mattingly, Deborah Morse, Michelle A. King, John D. Iwaniec, Jamal M. Alzahrani, Thomas L. Clanton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/00a910c9bab542beb23621aebc00bfec
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spelling	oai:doaj.org-article:00a910c9bab542beb23621aebc00bfec2021-12-02T14:23:18ZSkeletal muscle fibers play a functional role in host defense during sepsis in mice10.1038/s41598-021-86585-52045-2322https://doaj.org/article/00a910c9bab542beb23621aebc00bfec2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86585-5https://doaj.org/toc/2045-2322Abstract Skeletal muscles secrete a wide variety of immunologically active cytokines, but the functional significance of this response to in vivo innate immunity is not understood. We addressed this by knocking out the toll receptor adapter protein, Myd88, only in skeletal muscle fibers (skmMyd88KO), and followed male and female mice at 6 and 12 h after peritoneal injection of cecal slurry (CS), a model of polymicrobial sepsis. Because of a previously identified increase in mortality to CS injection, males received ~ 30% lower dose. At 12 h, skmMyd88KO caused significant reductions in a wide variety of pro- and anti-inflammatory plasma cytokines, e.g. TNFα, IL-1β and IL-10, compared to strain-matched controls in both males and females. Similar reductions were observed at 6 h in females. SkmMyd88KO led to ~ 40–50% elevations in peritoneal neutrophils at 6 and 12 h post CS in females. At 12 h post CS, skmMyd88KO increased peritoneal monocytes/macrophages and decreased %eosinophils and %basophils in females. SkmMyd88KO also led to significantly higher rates of mortality in female mice but not in males. In conclusion, the results suggest that skeletal muscle Myd88-dependent signal transduction can play functionally important role in normal whole body, innate immune inflammatory responses to peritoneal sepsis.Orlando LaitanoGerard P. RobinsonKevin O. MurrayChristian K. GarciaAlex J. MattinglyDeborah MorseMichelle A. KingJohn D. IwaniecJamal M. AlzahraniThomas L. ClantonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Orlando Laitano Gerard P. Robinson Kevin O. Murray Christian K. Garcia Alex J. Mattingly Deborah Morse Michelle A. King John D. Iwaniec Jamal M. Alzahrani Thomas L. Clanton Skeletal muscle fibers play a functional role in host defense during sepsis in mice
description	Abstract Skeletal muscles secrete a wide variety of immunologically active cytokines, but the functional significance of this response to in vivo innate immunity is not understood. We addressed this by knocking out the toll receptor adapter protein, Myd88, only in skeletal muscle fibers (skmMyd88KO), and followed male and female mice at 6 and 12 h after peritoneal injection of cecal slurry (CS), a model of polymicrobial sepsis. Because of a previously identified increase in mortality to CS injection, males received ~ 30% lower dose. At 12 h, skmMyd88KO caused significant reductions in a wide variety of pro- and anti-inflammatory plasma cytokines, e.g. TNFα, IL-1β and IL-10, compared to strain-matched controls in both males and females. Similar reductions were observed at 6 h in females. SkmMyd88KO led to ~ 40–50% elevations in peritoneal neutrophils at 6 and 12 h post CS in females. At 12 h post CS, skmMyd88KO increased peritoneal monocytes/macrophages and decreased %eosinophils and %basophils in females. SkmMyd88KO also led to significantly higher rates of mortality in female mice but not in males. In conclusion, the results suggest that skeletal muscle Myd88-dependent signal transduction can play functionally important role in normal whole body, innate immune inflammatory responses to peritoneal sepsis.
format	article
author	Orlando Laitano Gerard P. Robinson Kevin O. Murray Christian K. Garcia Alex J. Mattingly Deborah Morse Michelle A. King John D. Iwaniec Jamal M. Alzahrani Thomas L. Clanton
author_facet	Orlando Laitano Gerard P. Robinson Kevin O. Murray Christian K. Garcia Alex J. Mattingly Deborah Morse Michelle A. King John D. Iwaniec Jamal M. Alzahrani Thomas L. Clanton
author_sort	Orlando Laitano
title	Skeletal muscle fibers play a functional role in host defense during sepsis in mice
title_short	Skeletal muscle fibers play a functional role in host defense during sepsis in mice
title_full	Skeletal muscle fibers play a functional role in host defense during sepsis in mice
title_fullStr	Skeletal muscle fibers play a functional role in host defense during sepsis in mice
title_full_unstemmed	Skeletal muscle fibers play a functional role in host defense during sepsis in mice
title_sort	skeletal muscle fibers play a functional role in host defense during sepsis in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/00a910c9bab542beb23621aebc00bfec
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Skeletal muscle fibers play a functional role in host defense during sepsis in mice

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