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.
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.
Linehan
Sheena A
SA
Sir William Dunn School of Pathology, South Parks Road, Oxford, London, United Kingdom. s.a.linehan@ic.ac.uk
Coulson
Patricia S
PS
Wilson
R Alan
RA
Mountford
Adrian P
AP
Brombacher
Frank
F
Martínez-Pomares
Luisa
L
Gordon
Siamon
S
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
D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D019948:Receptors, Interleukin-4