CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition

Abstract Agonist interaction with Toll-like receptors (TLRs) induces T cell-mediated immunity, which is effective against intracellular pathogens. Consequently, TLR agonists are being tried as immunomodulatory agents. The lectin ArtinM targets TLR2 N-glycans on macrophages, induces cytokines product...

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Autores principales:	Thiago Aparecido da Silva, André L. V. Zorzetto-Fernandes, Nerry T. Cecílio, Aline Sardinha-Silva, Fabrício Freitas Fernandes, Maria Cristina Roque-Barreira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d593359256734f0a91f5320af60e7590
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spelling	oai:doaj.org-article:d593359256734f0a91f5320af60e75902021-12-02T11:53:10ZCD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition10.1038/s41598-017-07397-02045-2322https://doaj.org/article/d593359256734f0a91f5320af60e75902017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07397-0https://doaj.org/toc/2045-2322Abstract Agonist interaction with Toll-like receptors (TLRs) induces T cell-mediated immunity, which is effective against intracellular pathogens. Consequently, TLR agonists are being tried as immunomodulatory agents. The lectin ArtinM targets TLR2 N-glycans on macrophages, induces cytokines production, and promotes T helper-1 immunity, a process that culminates in resistance to several parasitic and fungal infections in vivo. Because co-receptors influence agonist binding to TLRs, we investigated whether CD14 is required for macrophage activation induced by ArtinM. Macrophages from wild-type mice stimulated by ArtinM not only produced cytokines but also had the following activation profile: (i) expression of M1 polarization markers; (ii) nitrite oxide production; (iii) cellular migration; (iv) enhanced phagocytic and fungicide activity; (v) modulation of TLR2 expression; and (vi) activation of NF-κB pathway. This activation profile induced by ArtinM was evaluated in macrophages lacking CD14 that showed none of the ArtinM effects. We demonstrated by immunoprecipitation and sugar inhibition assays the physical interaction of ArtinM, TLR2, and CD14, which depends on recognition of the trimannoside that constitutes the core of N-glycans. Thus, our study showed that CD14 is critical for ArtinM-induced macrophage activation, providing fundamental insight into the design of anti-infective therapies based on carbohydrate recognition.Thiago Aparecido da SilvaAndré L. V. Zorzetto-FernandesNerry T. CecílioAline Sardinha-SilvaFabrício Freitas FernandesMaria Cristina Roque-BarreiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thiago Aparecido da Silva André L. V. Zorzetto-Fernandes Nerry T. Cecílio Aline Sardinha-Silva Fabrício Freitas Fernandes Maria Cristina Roque-Barreira CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition
description	Abstract Agonist interaction with Toll-like receptors (TLRs) induces T cell-mediated immunity, which is effective against intracellular pathogens. Consequently, TLR agonists are being tried as immunomodulatory agents. The lectin ArtinM targets TLR2 N-glycans on macrophages, induces cytokines production, and promotes T helper-1 immunity, a process that culminates in resistance to several parasitic and fungal infections in vivo. Because co-receptors influence agonist binding to TLRs, we investigated whether CD14 is required for macrophage activation induced by ArtinM. Macrophages from wild-type mice stimulated by ArtinM not only produced cytokines but also had the following activation profile: (i) expression of M1 polarization markers; (ii) nitrite oxide production; (iii) cellular migration; (iv) enhanced phagocytic and fungicide activity; (v) modulation of TLR2 expression; and (vi) activation of NF-κB pathway. This activation profile induced by ArtinM was evaluated in macrophages lacking CD14 that showed none of the ArtinM effects. We demonstrated by immunoprecipitation and sugar inhibition assays the physical interaction of ArtinM, TLR2, and CD14, which depends on recognition of the trimannoside that constitutes the core of N-glycans. Thus, our study showed that CD14 is critical for ArtinM-induced macrophage activation, providing fundamental insight into the design of anti-infective therapies based on carbohydrate recognition.
format	article
author	Thiago Aparecido da Silva André L. V. Zorzetto-Fernandes Nerry T. Cecílio Aline Sardinha-Silva Fabrício Freitas Fernandes Maria Cristina Roque-Barreira
author_facet	Thiago Aparecido da Silva André L. V. Zorzetto-Fernandes Nerry T. Cecílio Aline Sardinha-Silva Fabrício Freitas Fernandes Maria Cristina Roque-Barreira
author_sort	Thiago Aparecido da Silva
title	CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition
title_short	CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition
title_full	CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition
title_fullStr	CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition
title_full_unstemmed	CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition
title_sort	cd14 is critical for tlr2-mediated m1 macrophage activation triggered by n-glycan recognition
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d593359256734f0a91f5320af60e7590
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_version_	1718394896625172480

CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition

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