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.
Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes / S. Varchetta, E. Brunetta, A. Roberto, J. Mikulak, K.L. Hudspeth, M.U. Mondelli, D. Mavilio. - In: PLOS ONE. - ISSN 1932-6203. - 7:9(2012), pp. e45821.1-e45821.12.
|Titolo:||Engagement of Siglec-7 receptor induces a pro-inflammatory response selectively in monocytes|
BRUNETTA, ENRICO (Secondo)
MAVILIO, DOMENICO (Corresponding)
|Parole Chiave:||antigens, CD; antigens, differentiation, myelomonocytic ; candida albicans; cell adhesion molecules; cells, cultured; cytokines; escherichia coli; extracellular signal-regulated MAP kinases; gene expression; gene expression regulation; host-pathogen interactions; humans; inflammation mediators; lectins; leukocytes, mononuclear; MAP kinase signaling system; phosphorylation; primary cell culture; protein binding; protein processing, post-translational; zymosan|
|Settore Scientifico Disciplinare:||Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio|
Settore MED/04 - Patologia Generale
Settore MED/17 - Malattie Infettive
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0045821|
|Appare nelle tipologie:||01 - Articolo su periodico|