Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.

Sialic acid binding immunoglobulin-like lectin-7 (Siglec-7) is a trans-membrane receptor carrying immunoreceptor tyrosine based inhibitory motifs (ITIMs) and delivering inhibitory signals upon ligation with sialylated glycans. This inhibitory function can be also targeted by several pathogens that h...

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Autores principales:	Stefania Varchetta, Enrico Brunetta, Alessandra Roberto, Joanna Mikulak, Kelly L Hudspeth, Mario U Mondelli, Domenico Mavilio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d8a4e505ab2e41188c85d6a56d60aa44
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spelling	oai:doaj.org-article:d8a4e505ab2e41188c85d6a56d60aa442021-11-18T07:04:03ZEngagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.1932-620310.1371/journal.pone.0045821https://doaj.org/article/d8a4e505ab2e41188c85d6a56d60aa442012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23029261/?tool=EBIhttps://doaj.org/toc/1932-6203Sialic acid binding immunoglobulin-like lectin-7 (Siglec-7) is a trans-membrane receptor carrying immunoreceptor tyrosine based inhibitory motifs (ITIMs) and delivering inhibitory signals upon ligation with sialylated glycans. This inhibitory function can be also targeted by several pathogens that have evolved to express sialic acids on their surface to escape host immune responses. Here, we demonstrate that cross-linking of Siglec-7 by a specific monoclonal antibody (mAb) induces a remarkably high production of IL-6, IL-1α, CCL4/MIP-1β, IL-8 and TNF-α. Among the three immune cell subsets known to constitutively express Siglec-7, the production of these pro-inflammatory cytokines and chemokines selectively occurs in monocytes and not in Natural Killer or T lymphocytes. This Siglec-7-mediated activating function is associated with the phosphorylation of the extracellular signal-regulated kinase (ERK) pathway. The present study also shows that sialic acid-free Zymosan yeast particles are able to bind Siglec-7 on monocytes and that this interaction mimics the ability of the anti Siglec-7 mAb to induce the production of pro-inflammatory mediators. Indeed, blocking or silencing Siglec-7 in primary monocytes greatly reduced the production of inflammatory cytokines and chemokines in response to Zymosan, thus confirming that Siglec-7 participates in generating a monocyte-mediated inflammatory outcome following pathogen recognition. The presence of an activating form of Siglec-7 in monocytes provides the host with a new and alternative mechanism to encounter pathogens not expressing sialylated glycans.Stefania VarchettaEnrico BrunettaAlessandra RobertoJoanna MikulakKelly L HudspethMario U MondelliDomenico MavilioPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45821 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stefania Varchetta Enrico Brunetta Alessandra Roberto Joanna Mikulak Kelly L Hudspeth Mario U Mondelli Domenico Mavilio Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.
description	Sialic acid binding immunoglobulin-like lectin-7 (Siglec-7) is a trans-membrane receptor carrying immunoreceptor tyrosine based inhibitory motifs (ITIMs) and delivering inhibitory signals upon ligation with sialylated glycans. This inhibitory function can be also targeted by several pathogens that have evolved to express sialic acids on their surface to escape host immune responses. Here, we demonstrate that cross-linking of Siglec-7 by a specific monoclonal antibody (mAb) induces a remarkably high production of IL-6, IL-1α, CCL4/MIP-1β, IL-8 and TNF-α. Among the three immune cell subsets known to constitutively express Siglec-7, the production of these pro-inflammatory cytokines and chemokines selectively occurs in monocytes and not in Natural Killer or T lymphocytes. This Siglec-7-mediated activating function is associated with the phosphorylation of the extracellular signal-regulated kinase (ERK) pathway. The present study also shows that sialic acid-free Zymosan yeast particles are able to bind Siglec-7 on monocytes and that this interaction mimics the ability of the anti Siglec-7 mAb to induce the production of pro-inflammatory mediators. Indeed, blocking or silencing Siglec-7 in primary monocytes greatly reduced the production of inflammatory cytokines and chemokines in response to Zymosan, thus confirming that Siglec-7 participates in generating a monocyte-mediated inflammatory outcome following pathogen recognition. The presence of an activating form of Siglec-7 in monocytes provides the host with a new and alternative mechanism to encounter pathogens not expressing sialylated glycans.
format	article
author	Stefania Varchetta Enrico Brunetta Alessandra Roberto Joanna Mikulak Kelly L Hudspeth Mario U Mondelli Domenico Mavilio
author_facet	Stefania Varchetta Enrico Brunetta Alessandra Roberto Joanna Mikulak Kelly L Hudspeth Mario U Mondelli Domenico Mavilio
author_sort	Stefania Varchetta
title	Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.
title_short	Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.
title_full	Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.
title_fullStr	Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.
title_full_unstemmed	Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.
title_sort	engagement of siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d8a4e505ab2e41188c85d6a56d60aa44
work_keys_str_mv	AT stefaniavarchetta engagementofsiglec7receptorinducesaproinflammatoryresponseselectivelyinmonocytes AT enricobrunetta engagementofsiglec7receptorinducesaproinflammatoryresponseselectivelyinmonocytes AT alessandraroberto engagementofsiglec7receptorinducesaproinflammatoryresponseselectivelyinmonocytes AT joannamikulak engagementofsiglec7receptorinducesaproinflammatoryresponseselectivelyinmonocytes AT kellylhudspeth engagementofsiglec7receptorinducesaproinflammatoryresponseselectivelyinmonocytes AT marioumondelli engagementofsiglec7receptorinducesaproinflammatoryresponseselectivelyinmonocytes AT domenicomavilio engagementofsiglec7receptorinducesaproinflammatoryresponseselectivelyinmonocytes
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Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes.

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