Role of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages.

Francisella tularensis is an infectious, gram-negative, intracellular microorganism, and the cause of tularemia. Invasion of host cells by intracellular pathogens like Francisella is initiated by their interaction with different host cell membrane receptors and the rapid phosphorylation of different...

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Autores principales:	Michael W Edwards, James A Aultman, Gregory Harber, Jay M Bhatt, Elizabeth Sztul, Qingan Xu, Ping Zhang, Suzanne M Michalek, Jannet Katz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ad295ef7f82c4337b82c8e80196a451f
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spelling	oai:doaj.org-article:ad295ef7f82c4337b82c8e80196a451f2021-11-18T08:43:41ZRole of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages.1932-620310.1371/journal.pone.0083226https://doaj.org/article/ad295ef7f82c4337b82c8e80196a451f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24312679/?tool=EBIhttps://doaj.org/toc/1932-6203Francisella tularensis is an infectious, gram-negative, intracellular microorganism, and the cause of tularemia. Invasion of host cells by intracellular pathogens like Francisella is initiated by their interaction with different host cell membrane receptors and the rapid phosphorylation of different downstream signaling molecules. PI3K and Syk have been shown to be involved in F. tularensis host cell entry, and both of these signaling molecules are associated with the master regulator serine/threonine kinase mTOR; yet the involvement of mTOR in F. tularensis invasion of host cells has not been assessed. Here, we report that infection of macrophages with F. tularensis triggers the phosphorylation of mTOR downstream effector molecules, and that signaling via TLR2 is necessary for these events. Inhibition of mTOR or of PI3K, ERK, or p38, but not Akt signaling, downregulates the levels of phosphorylation of mTOR downstream targets, and significantly reduces the number of F. tularensis cells invading macrophages. Moreover, while phosphorylation of mTOR downstream effectors occurs via the PI3K pathway, it also involves PLCγ1 and Ca(2+) signaling. Furthermore, abrogation of PLC or Ca(2+) signaling revealed their important role in the ability of F. tularensis to invade host cells. Together, these findings suggest that F. tularensis invasion of primary macrophages utilize a myriad of host signaling pathways to ensure effective cell entry.Michael W EdwardsJames A AultmanGregory HarberJay M BhattElizabeth SztulQingan XuPing ZhangSuzanne M MichalekJannet KatzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83226 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael W Edwards James A Aultman Gregory Harber Jay M Bhatt Elizabeth Sztul Qingan Xu Ping Zhang Suzanne M Michalek Jannet Katz Role of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages.
description	Francisella tularensis is an infectious, gram-negative, intracellular microorganism, and the cause of tularemia. Invasion of host cells by intracellular pathogens like Francisella is initiated by their interaction with different host cell membrane receptors and the rapid phosphorylation of different downstream signaling molecules. PI3K and Syk have been shown to be involved in F. tularensis host cell entry, and both of these signaling molecules are associated with the master regulator serine/threonine kinase mTOR; yet the involvement of mTOR in F. tularensis invasion of host cells has not been assessed. Here, we report that infection of macrophages with F. tularensis triggers the phosphorylation of mTOR downstream effector molecules, and that signaling via TLR2 is necessary for these events. Inhibition of mTOR or of PI3K, ERK, or p38, but not Akt signaling, downregulates the levels of phosphorylation of mTOR downstream targets, and significantly reduces the number of F. tularensis cells invading macrophages. Moreover, while phosphorylation of mTOR downstream effectors occurs via the PI3K pathway, it also involves PLCγ1 and Ca(2+) signaling. Furthermore, abrogation of PLC or Ca(2+) signaling revealed their important role in the ability of F. tularensis to invade host cells. Together, these findings suggest that F. tularensis invasion of primary macrophages utilize a myriad of host signaling pathways to ensure effective cell entry.
format	article
author	Michael W Edwards James A Aultman Gregory Harber Jay M Bhatt Elizabeth Sztul Qingan Xu Ping Zhang Suzanne M Michalek Jannet Katz
author_facet	Michael W Edwards James A Aultman Gregory Harber Jay M Bhatt Elizabeth Sztul Qingan Xu Ping Zhang Suzanne M Michalek Jannet Katz
author_sort	Michael W Edwards
title	Role of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages.
title_short	Role of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages.
title_full	Role of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages.
title_fullStr	Role of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages.
title_full_unstemmed	Role of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages.
title_sort	role of mtor downstream effector signaling molecules in francisella tularensis internalization by murine macrophages.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ad295ef7f82c4337b82c8e80196a451f
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Role of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages.

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