CD209a Synergizes with Dectin-2 and Mincle to Drive Severe Th17 Cell-Mediated Schistosome Egg-Induced Immunopathology

Parisa Kalantari, Yoelkys Morales, Emily A. Miller, Luis D. Jaramillo, Holly E. Ponichtera, Marcel A. Wuethrich, Cheolho Cheong, Maria C. Seminario, Joanne M. Russo, Stephen C. Bunnell, Miguel J. Stadecker

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1β and IL-23 produced by dendritic cells that express CD209a (SIGNR5), a C-type lectin receptor (CLR) related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe immunopathology. In vitro, CD209a augments the egg-induced IL-1β and IL-23 production initiated by the related CLRs Dectin-2 and Mincle. While Dectin-2 and Mincle trigger an FcRγ-dependent signaling cascade that involves the tyrosine kinase Syk and the trimolecular Card9-Bcl10-Malt1 complex, CD209a promotes the sustained activation of Raf-1. Our findings demonstrate that CD209a drives severe Th17 cell-mediated immunopathology in a helminthic disease based on synergy between DC-SIGN- and Dectin-2-related CLRs. Kalantari et al. demonstrate the role of CD209a (SIGNR5) in the development of Th17 cell-mediated immunopathology in murine schistosomiasis. CD209a drives proinflammatory cytokine production in synergy with Dectin-2 and Mincle, each acting via distinct signaling pathways. These findings denote C-type lectin receptor cross talk resulting in severe helminthic disease.

Original languageEnglish (US)
Pages (from-to)1288-1300
Number of pages13
JournalCell Reports
Volume22
Issue number5
DOIs
StatePublished - Jan 30 2018

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

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