Journal
LABORATORY INVESTIGATION
Volume 83, Issue 8, Pages 1223-1231Publisher
NATURE PUBLISHING GROUP
DOI: 10.1097/01.LAB.0000081392.93701.6F
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High levels of mannose receptor (MR) expression and pinocytic activity are a hallmark of Th2 cytokine-driven alternative MPhi activation in vitro. We examined expression of MR in situ and its regulation by Th1/Th2 cytokines in IL-4Ralpha -/- and wild-type (WT) mice challenged with Schistosoma mansoni. Parasite eggs induce a vigorous granulomatous response, driven by Th2 cytokines in WT mice, but by Th1 cytokines in IL-4Ra -/- mice. MR was expressed by granuloma MPhi in WT mice but not in IL-4Ralpha -/- mice, whose MPhi nevertheless exhibited a mature phenotype and morphology. By contrast expression of MR in resident tissue MPhi and endothelial cells appeared unaffected by Th1/Th2 cytokines. Our results revealed that Th1/Th2 cytokines differentially regulate MR according to cell type and play a critical role in regulating MR expression by MPhi recruited to granulomata. We also present evidence that components of schistosome eggs and a fraction of their secretions are ligands of MR, and suggest that MR activity may be of functional significance in the granulomatous response.
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