High levels of mannose receptor (MR) expression and pinocytic activity are a hallmark of Th2 cytokine-driven alternative MΦ activation in vitro. We examined expression of MR in situ and its regulation by Th1/Th2 cytokines in IL-4Rα −/− 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-4Rα −/− mice. MR was expressed by granuloma MΦ in WT mice but not in IL-4Rα −/− mice, whose MΦ nevertheless exhibited a mature phenotype and morphology. By contrast expression of MR in resident tissue MΦ 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 MΦ 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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We thank Mrs. Liz Darley for histology support, Dr. Peter D. Ashton for providing SEA and ESP, and Dr. Delyth M. Reid for preparing MR5D3 mAb.
This work was supported by Grant No. G0525 from the Arthritis Research Campaign and a Junior Research Fellowship from St. Cross College, Oxford (SAL). Support was also received from the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (PSC, RAW), and Program Grant No. G8303179 from the Medical Research Council, United Kingdom (SG).
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