Dendritic cell expression of the C-type lectin receptor CD209a: A novel innate parasite-sensing mechanism inducing Th17 cells that drive severe immunopathology in murine schistosome infection.

Abstract

Following infection with the trematode helminth Schistosoma mansoni, CBA mice develop severe parasite egg-induced hepatic granulomatous inflammation as well as prominent CD4(+) T helper 17 (Th17) cell responses driven by dendritic cell (DC)-derived IL-1β and IL-23. By comparison, C57BL/6 mice develop mild hepatic immunopathology, egg stimulation of DCs does not result in IL-1β and IL-23 production, and Th17 cells fail to develop. To investigate the reasons for strain-specific differences in antigen presenting cell (APC) reactivity to eggs, we performed a comparative gene profiling analysis of normal bone marrow-derived DCs (BMDCs) and found that CBA DCs display markedly elevated expression of C-type lectin receptors (CLRs). In particular, expression of CD209a, a murine homologue of human DC-specific ICAM-3-grabbing non-integrin (DC-SIGN, CD209), was strikingly higher in CBA than BL/6 DCs. High CD209a surface expression was observed in various CBA splenic and granuloma APC subpopulations; however, only DCs, and not macrophages, B cells or neutrophils, were able to induce Th17 cell differentiation in response to schistosome eggs. Lentiviral gene silencing in CBA DCs, and over-expression in BL/6 DCs, demonstrated CD209a to be critical for egg-induced DC IL-1β and IL-23 production necessary for Th17 cell differentiation and expansion. These findings reveal a novel innate parasite-sensing mechanism promoting CD4(+) Th17 cells that mediate severe immunopathology in schistosomiasis.

• Authors: Holly E Ponichtera, Miguel J Stadecker
• Journal: Experimental parasitology (Exp Parasitol) Vol. 158 Pg. 42-7 (Nov 2015) ISSN: 1090-2449 [Electronic] United States
• PMID: 25913088 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Cell Adhesion Molecules
• DC-specific ICAM-3 grabbing nonintegrin
• IL1B protein, mouse
• Interleukin-1beta
• Interleukin-23
• Lectins, C-Type
• Receptors, Cell Surface

Topics

• Adaptive Immunity
• Animals
• Cell Adhesion Molecules (metabolism)
• Dendritic Cells (immunology)
• Disease Models, Animal
• Granuloma (immunology, pathology)
• Immunity, Innate
• Interleukin-1beta (metabolism)
• Interleukin-23 (metabolism)
• Lectins, C-Type (metabolism)
• Mice
• Mice, Inbred CBA
• Receptors, Cell Surface (metabolism)
• Schistosomiasis mansoni (immunology, pathology)
• Signal Transduction
• Spleen (cytology, immunology)
• Th17 Cells (immunology)