title: IL-4 receptor signaling is required for mannose receptor expression by macrophages recruited to granulomata but not resident cells in mice infected with Schistosoma mansoni.
abstract: 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-4Ralpha -/- 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.
authors.affiliation: Sir William Dunn School of Pathology, South Parks Road, Oxford, London, United Kingdom. s.a.linehan@ic.ac.uk
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Linehan
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Coulson
authors.forename: R Alan
authors.initials: RA
authors.lastname: Wilson
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Mountford
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: Luisa
authors.initials: L
authors.lastname: Martínez-Pomares
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006099:Granuloma / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010063:Ovum / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D019948:Receptors, Interleukin-4