Dendritic cell CD209a expression is critical for the development of pathogenic Th17 cell responses in murine schistosomiasis (INC9P.443)

• Published in: The Journal of immunology (1950) 2014-05, Vol.192 (1_Supplement), p.188-188.2
• Main Authors: Ponichtera, Holly, Shainheit, Mara, Liu, Beiyun, Raychowdhury, Raktima, Larkin, Bridget, Russo, Joanne, Salantes, Danielle, Lai, Chao-Qiang, Parnell, Laurence, Yun, Tae, Cheong, Cheolho, Bunnell, Stephen, Hacohen, Nir, Stadecker, Miguel
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.188.2

The magnitude of immunopathology and pro-inflammatory cytokine production in murine Schistosoma mansoni infection is strain-dependent. Severe hepatic egg-induced granulomatous inflammation in CBA mice is associated with Th1 and Th17 cytokine responses, whereas BL/6 mice develop milder lesions in a Th2-polarized cytokine environment. Pathogenic Th17 cell responses in CBA mice are dependent on the production of IL-1β and IL-23 by egg-stimulated dendritic cells (DC); by comparison, such Th17 cells fail to develop in BL/6 mice. The reasons for strain-dependent differences in DC reactivity to eggs remain unclear. Genome-wide gene profiling revealed significant differences between CBA vs. BL/6 DCs in C-type lectin receptors (CLRs), a family of pattern recognition receptors that binds glycans such as those produced by schistosome eggs. Expression of the CLR CD209a, a murine homologue of human DC-specific ICAM-3-grabbing non-integrin (DC-SIGN), was strikingly higher in several APC populations from CBA mice; however, only CBA DC, but not macrophages, B cells, or granulocytes elicited Th17 cell differentiation in response to schistosome eggs. Gene silencing in CBA DC, and over-expression in BL/6 DC, demonstrated CD209a to be necessary for egg-induced DC production of ERK1/2 map kinase-dependent IL-1β and IL-23 as well as subsequent Th17 cell development. These findings reveal a novel mechanism controlling the development of Th17 cell-mediated immunopathology in helminthic disease.