Concurrent bacterial stimulation alters the function of helminth-activated dendritic cells, resulting in IL-17 induction

Perona-Wright, G. , Lundie, R. J., Jenkins, S. J., Webb, L. M., Grencis, R. K. and MacDonald, A. S. (2012) Concurrent bacterial stimulation alters the function of helminth-activated dendritic cells, resulting in IL-17 induction. Journal of Immunology, 188(5), pp. 2350-2358. (doi: 10.4049/jimmunol.1101642) (PMID:22287718) (PMCID:PMC3378507)

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Abstract

Infection with schistosome helminths is associated with granulomatous inflammation that forms around parasite eggs trapped in host tissues. In severe cases, the resulting fibrosis can lead to organ failure, portal hypertension, and fatal bleeding. Murine studies identified IL-17 as a critical mediator of this immunopathology, and mouse strains that produce high levels of IL-17 in response to schistosome infection show increased mortality. In this article, we demonstrate that schistosome-specific IL-17 induction by dendritic cells from low-pathology C57BL/6 mice is normally regulated by their concomitant induction of IL-10. Simultaneous stimulation of schistosome-exposed C57BL/6 dendritic cells with a heat-killed bacterium enabled these cells to overcome IL-10 regulation and induce IL-17, even in wild-type C57BL/6 recipients. This schistosome-specific IL-17 was dependent on IL-6 production by the copulsed dendritic cells. Coimmunization of C57BL/6 animals with bacterial and schistosome Ags also resulted in schistosome-specific IL-17, and this response was enhanced in the absence of IL-10–mediated immune regulation. Together, our data suggest that the balance of pro- and anti-inflammatory cytokines that determines the severity of pathology during schistosome infection can be influenced not only by host and parasite, but also by concurrent bacterial stimulation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Perona-Wright, Dr Georgia
Authors: Perona-Wright, G., Lundie, R. J., Jenkins, S. J., Webb, L. M., Grencis, R. K., and MacDonald, A. S.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606
Published Online:17 February 2012

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