Differential c-type lectin receptor expression correlates with the magnitude of pathology in murine schistosomiasis (55.4)

Abstract

Abstract In murine schistosomiasis, immunopathology and cytokine production in response to schistosome eggs is uneven and strain dependent. Infected CBA mice develop severe hepatic egg-induced granulomatous inflammation associated with prominent Th17 and Th1 cytokine responses, whereas in BL/6 mice milder lesions develop in a Th2-dominant cytokine environment. The pathogenic Th17 response in CBA mice is largely dependent on IL-1β and IL-23 produced by schistosome egg-stimulated dendritic cells (DC); by comparison, this pro-inflammatory cytokine pathway fails to materialize in low-pathology BL/6 mice. Whereas requirements for Th17 cell differentiation elicited by CBA DC are apparent, the reason for such a strain difference in APC reactivity to live eggs is not known. Initial gene profiling disclosed a significant difference in C-type lectin receptor (CLR) expression between CBA and BL/6 bone marrow derived DC. CLR are pattern recognition receptors capable of binding carbohydrates, including those secreted by schistosome eggs. A significant increase in CLR expression, particularly murine homologues of human DC-specific ICAM-3-grabbing non-integrin (DC-SIGN), was documented by real-time PCR and flow cytometry on tissues from infected CBA mice, including liver, spleen and granuloma cells. Current work is aimed at elucidating the functional implications of differential CLR expression on T cell subset differentiation, activation and pathogenicity during the schistosome infection.