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CD209a Expression on Dendritic Cells Is Critical for the Development of Pathogenic Th17 Cell Responses in Murine Schistosomiasis
- Source :
- The Journal of Immunology. 192:4655-4665
- Publication Year :
- 2014
- Publisher :
- The American Association of Immunologists, 2014.
-
Abstract
- In murine schistosomiasis, immunopathology and cytokine production in response to parasite eggs are uneven and strain dependent. CBA/J (CBA) mice develop severe hepatic granulomatous inflammation associated with prominent Th17 cell responses driven by dendritic cell (DC)-derived IL-1β and IL-23. Such Th17 cells fail to develop in low-pathology C57BL/6 (BL/6) mice, and the reasons for these strain-specific differences in APC reactivity to eggs remain unclear. We show by gene profiling that CBA DCs display an 18-fold higher expression of the C-type lectin receptor CD209a, a murine homolog of human DC-specific ICAM-3–grabbing nonintegrin, compared with BL/6 DCs. Higher CD209a expression was observed in CBA splenic and granuloma APC subpopulations, but only DCs induced Th17 cell differentiation in response to schistosome eggs. Gene silencing in CBA DCs and overexpression in BL/6 DCs demonstrated that CD209a is essential for egg-elicited IL-1β and IL-23 production and subsequent Th17 cell development, which is associated with SRC, RAF-1, and ERK1/2 activation. These findings reveal a novel mechanism controlling the development of Th17 cell–mediated severe immunopathology in helminthic disease.
- Subjects :
- MAP Kinase Signaling System
Cellular differentiation
medicine.medical_treatment
Interleukin-1beta
Proto-Oncogene Proteins pp60(c-src)
Immunology
Cell
Receptors, Cell Surface
Biology
Interleukin-23
Article
Cell Line
Mice
Immunopathology
medicine
Animals
Humans
Schistosomiasis
Immunology and Allergy
Gene silencing
Lectins, C-Type
Gene Silencing
Granuloma
Mitogen-Activated Protein Kinase 3
Cell growth
Dendritic Cells
Dendritic cell
Cell biology
Enzyme Activation
Proto-Oncogene Proteins c-raf
medicine.anatomical_structure
Cytokine
Gene Expression Regulation
Cell culture
Mice, Inbred CBA
Schistosoma
Th17 Cells
Female
Cell Adhesion Molecules
Spleen
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 192
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....0a53396d4eef522b76826a9efc578f3d