2026-04-29T04:52:18Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/66802024-10-31T11:53:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Kaiser, Maria M. M.
author
Ritter, Manuel
author
del Fresno, Carlos
author
Jonesdottir, Hulda S.
author
van der Ham, Alwin J.
author
Pelgrom, Leonard R.
author
Schramm, Gabriele
author
Leyland, Laura E.
author
Sancho, David
author
da Costa, Clarissa Prazeres
author
Giere, Martin
author
Yazdanbakhsh, Maria
author
Everts, Bart
funder
Indonesian Directorate of Higher Education
funder
Leiden University Medical Center
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Comisión Europea
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Asociación Española Contra el Cáncer
2018-11-22T08:10:52Z
2018-11-22T08:10:52Z
2018
PLoS Biol. 2018; 16(4):e2005504
1545-7885
http://hdl.handle.net/20.500.12105/6680
29668708
10.1371/journal.pbio.2005504
PLoS Biology
The molecular mechanisms through which dendritic cells (DCs) prime T helper 2 (Th2) responses, including those elicited by parasitic helminths, remain incompletely understood. Here, we report that soluble egg antigen (SEA) from Schistosoma mansoni, which is well known to drive potent Th2 responses, triggers DCs to produce prostaglandin E2 (PGE(2)), which subsequently-in an autocrine manner-induces OX40 ligand (OX40L) expression to license these DCs to drive Th2 responses. Mechanistically, SEA was found to promote PGE(2) synthesis through Dectin-1 and Dectin-2, and via a downstream signaling cascade involving spleen tyrosine kinase (Syk), extracellular signal-regulated kinase (ERK), cytosolic phospholipase A(2) (cPLA(2)), and cyclooxygenase 1 and 2 (COX-1 and COX-2). In addition, this pathway was activated independently of the actions of omega-1 (omega-1), a previously described Th2-priming glycoprotein present in SEA. These findings were supported by in vivo murine data showing that w-1 independent Th2 priming by SEA was mediated by Dectin-2 and Syk signaling in DCs. Finally, we found that Dectin-2(-/-), and to a lesser extent Dectin-1(-/-) mice, displayed impaired Th2 responses and reduced egg-driven granuloma formation following S. mansoni infection, highlighting the physiological importance of this pathway in Th2 polarization during a helminth infection. In summary, we identified a novel pathway in DCs involving Dectin-1/2-Syk-PGE(2)-OX40L through which Th2 immune responses are induced.
eng
Dectin-1/2-induced autocrine PGE(2) signaling licenses dendritic cells to prime Th2 responses
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