Mouse primary microglia respond differently to LPS and poly(I:C) in vitro

Abstract Microglia, CNS resident innate immune cells, respond strongly to activation of TLR3 and TLR4, which recognize viral dsRNA poly(I:C) and bacterial endotoxin LPS, respectively. However, few studies have thoroughly and parallelly compared functional phenotypes and downstream mechanisms between...

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Autores principales:	Yingbo He, Natalie Taylor, Xiang Yao, Anindya Bhattacharya
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71eb2cdc93b4460cb1a03ab83fade020
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spelling	oai:doaj.org-article:71eb2cdc93b4460cb1a03ab83fade0202021-12-02T15:45:16ZMouse primary microglia respond differently to LPS and poly(I:C) in vitro10.1038/s41598-021-89777-12045-2322https://doaj.org/article/71eb2cdc93b4460cb1a03ab83fade0202021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89777-1https://doaj.org/toc/2045-2322Abstract Microglia, CNS resident innate immune cells, respond strongly to activation of TLR3 and TLR4, which recognize viral dsRNA poly(I:C) and bacterial endotoxin LPS, respectively. However, few studies have thoroughly and parallelly compared functional phenotypes and downstream mechanisms between LPS- and poly(I:C)-exposed primary microglia. Here, we investigated the responses of mouse primary microglia upon LPS and poly(I:C) stimulation by detecting various phenotypes ranging from morphology, proliferation, secretion, chemotaxis, to phagocytosis. Furthermore, we explored their sequential gene expression and the downstream signal cascades. Interestingly, we found that the microglial activation pattern induced by LPS was distinguished from that induced by poly(I:C). Regarding microglial morphology, LPS caused an ameboid-like shape while poly(I:C) induced a bushy shape. Microglial proliferation was also facilitated by LPS but not by poly(I:C). In addition, LPS and poly(I:C) modulated microglial chemotaxis and phagocytosis differently. Furthermore, genome-wide analysis provided gene-level support to these functional differences, which may be associated with NF-κb and type I interferon pathways. Last, LPS- and poly(I:C)-activated microglia mediated neurotoxicity in a co-culture system. This study extends our understanding of TLR roles in microglia and provides insights into selecting proper inflammatory microglial models, which may facilitate identification of new targets for therapeutic application.Yingbo HeNatalie TaylorXiang YaoAnindya BhattacharyaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yingbo He Natalie Taylor Xiang Yao Anindya Bhattacharya Mouse primary microglia respond differently to LPS and poly(I:C) in vitro
description	Abstract Microglia, CNS resident innate immune cells, respond strongly to activation of TLR3 and TLR4, which recognize viral dsRNA poly(I:C) and bacterial endotoxin LPS, respectively. However, few studies have thoroughly and parallelly compared functional phenotypes and downstream mechanisms between LPS- and poly(I:C)-exposed primary microglia. Here, we investigated the responses of mouse primary microglia upon LPS and poly(I:C) stimulation by detecting various phenotypes ranging from morphology, proliferation, secretion, chemotaxis, to phagocytosis. Furthermore, we explored their sequential gene expression and the downstream signal cascades. Interestingly, we found that the microglial activation pattern induced by LPS was distinguished from that induced by poly(I:C). Regarding microglial morphology, LPS caused an ameboid-like shape while poly(I:C) induced a bushy shape. Microglial proliferation was also facilitated by LPS but not by poly(I:C). In addition, LPS and poly(I:C) modulated microglial chemotaxis and phagocytosis differently. Furthermore, genome-wide analysis provided gene-level support to these functional differences, which may be associated with NF-κb and type I interferon pathways. Last, LPS- and poly(I:C)-activated microglia mediated neurotoxicity in a co-culture system. This study extends our understanding of TLR roles in microglia and provides insights into selecting proper inflammatory microglial models, which may facilitate identification of new targets for therapeutic application.
format	article
author	Yingbo He Natalie Taylor Xiang Yao Anindya Bhattacharya
author_facet	Yingbo He Natalie Taylor Xiang Yao Anindya Bhattacharya
author_sort	Yingbo He
title	Mouse primary microglia respond differently to LPS and poly(I:C) in vitro
title_short	Mouse primary microglia respond differently to LPS and poly(I:C) in vitro
title_full	Mouse primary microglia respond differently to LPS and poly(I:C) in vitro
title_fullStr	Mouse primary microglia respond differently to LPS and poly(I:C) in vitro
title_full_unstemmed	Mouse primary microglia respond differently to LPS and poly(I:C) in vitro
title_sort	mouse primary microglia respond differently to lps and poly(i:c) in vitro
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/71eb2cdc93b4460cb1a03ab83fade020
work_keys_str_mv	AT yingbohe mouseprimarymicrogliaresponddifferentlytolpsandpolyicinvitro AT natalietaylor mouseprimarymicrogliaresponddifferentlytolpsandpolyicinvitro AT xiangyao mouseprimarymicrogliaresponddifferentlytolpsandpolyicinvitro AT anindyabhattacharya mouseprimarymicrogliaresponddifferentlytolpsandpolyicinvitro
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Mouse primary microglia respond differently to LPS and poly(I:C) in vitro

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