Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.

Mycobacteria develop strategies to evade the host immune system. Among them, mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode of action of PIM anti-inflammatory effects. Synthetic PIM(1)...

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Autores principales:	Nathalie Court, Stéphanie Rose, Marie-Laure Bourigault, Sophie Front, Olivier R Martin, Jennifer K Dowling, Elaine F Kenny, Luke O'Neill, François Erard, Valerie F J Quesniaux
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6af7d97d62e44674902b88aab5c3e670
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spelling	oai:doaj.org-article:6af7d97d62e44674902b88aab5c3e6702021-11-04T06:08:24ZMycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.1932-620310.1371/journal.pone.0024631https://doaj.org/article/6af7d97d62e44674902b88aab5c3e6702011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21949737/?tool=EBIhttps://doaj.org/toc/1932-6203Mycobacteria develop strategies to evade the host immune system. Among them, mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode of action of PIM anti-inflammatory effects. Synthetic PIM(1) isomer and PIM(2) mimetic potently inhibit TNF and IL-12 p40 expression induced by TLR2 or TLR4 pathways, but not by TLR9, in murine macrophages. We show inhibition of LPS binding to TLR4/MD2/CD14 expressing HEK cells by PIM(1) and PIM(2) analogues. More specifically, the binding of LPS to CD14 was inhibited by PIM(1) and PIM(2) analogues. CD14 was dispensable for PIM(1) and PIM(2) analogues functional inhibition of TLR2 agonists induced TNF, as shown in CD14-deficient macrophages. The use of rough-LPS, that stimulates TLR4 pathway independently of CD14, allowed to discriminate between CD14-dependent and CD14-independent anti-inflammatory effects of PIMs on LPS-induced macrophage responses. PIM(1) and PIM(2) analogues inhibited LPS-induced TNF release by a CD14-dependent pathway, while IL-12 p40 inhibition was CD14-independent, suggesting that PIMs have multifold inhibitory effects on the TLR4 signalling pathway.Nathalie CourtStéphanie RoseMarie-Laure BourigaultSophie FrontOlivier R MartinJennifer K DowlingElaine F KennyLuke O'NeillFrançois ErardValerie F J QuesniauxPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24631 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nathalie Court Stéphanie Rose Marie-Laure Bourigault Sophie Front Olivier R Martin Jennifer K Dowling Elaine F Kenny Luke O'Neill François Erard Valerie F J Quesniaux Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.
description	Mycobacteria develop strategies to evade the host immune system. Among them, mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode of action of PIM anti-inflammatory effects. Synthetic PIM(1) isomer and PIM(2) mimetic potently inhibit TNF and IL-12 p40 expression induced by TLR2 or TLR4 pathways, but not by TLR9, in murine macrophages. We show inhibition of LPS binding to TLR4/MD2/CD14 expressing HEK cells by PIM(1) and PIM(2) analogues. More specifically, the binding of LPS to CD14 was inhibited by PIM(1) and PIM(2) analogues. CD14 was dispensable for PIM(1) and PIM(2) analogues functional inhibition of TLR2 agonists induced TNF, as shown in CD14-deficient macrophages. The use of rough-LPS, that stimulates TLR4 pathway independently of CD14, allowed to discriminate between CD14-dependent and CD14-independent anti-inflammatory effects of PIMs on LPS-induced macrophage responses. PIM(1) and PIM(2) analogues inhibited LPS-induced TNF release by a CD14-dependent pathway, while IL-12 p40 inhibition was CD14-independent, suggesting that PIMs have multifold inhibitory effects on the TLR4 signalling pathway.
format	article
author	Nathalie Court Stéphanie Rose Marie-Laure Bourigault Sophie Front Olivier R Martin Jennifer K Dowling Elaine F Kenny Luke O'Neill François Erard Valerie F J Quesniaux
author_facet	Nathalie Court Stéphanie Rose Marie-Laure Bourigault Sophie Front Olivier R Martin Jennifer K Dowling Elaine F Kenny Luke O'Neill François Erard Valerie F J Quesniaux
author_sort	Nathalie Court
title	Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.
title_short	Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.
title_full	Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.
title_fullStr	Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.
title_full_unstemmed	Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.
title_sort	mycobacterial pims inhibit host inflammatory responses through cd14-dependent and cd14-independent mechanisms.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/6af7d97d62e44674902b88aab5c3e670
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Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.

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