IL-4R alpha expression by bone marrow-derived cells is necessary and sufficient for host protection against acute schistosomiasis.
IL 4 receptor alpha (IL-4Ralpha) expression by non-bone marrow (BM)-derived cells is required to protect hosts against several parasitic helminth species. In contrast, we demonstrate that IL-4Ralpha expression by BM-derived cells is both necessary and sufficient to prevent Schistosoma mansoni-infected mice from developing severe inflammation directed against parasite ova, whereas IL-4Ralpha expression by non-BM-derived cells is neither necessary nor sufficient. Chimeras that express IL-4Ralpha only on non-BM-derived cells still produce Th2 cytokines, but overproduce IL-12p40, TNF, and IFN-gamma, fail to generate alternatively activated macrophages, and develop endotoxemia and severe hepatic and intestinal pathology. In contrast, chimeras that express IL-4Ralpha only on BM-derived cells have extended survival, even though the granulomas that they develop around parasite eggs are small and devoid of collagen. These observations identify distinct roles for IL-4/IL-13 responsive cell lineages during schistosomiasis: IL-4Ralpha-mediated signaling in non-BM-derived cells regulates granuloma size and fibrosis, whereas signaling in BM-derived cells suppresses parasite egg-driven inflammation within the liver and intestine.
Herbert
De'Broski R
DR
Research Service (151), Cincinnati Veterans Administration Medical Center, Cincinnati, OH 45220, USA.
Orekov
Tatyana
T
Perkins
Charles
C
Rothenberg
Marc E
ME
Finkelman
Fred D
FD
D000208:Acute Disease; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D006099:Granuloma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053662:Interleukin-4 Receptor alpha Subunit / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology
D053662:Interleukin-4 Receptor alpha Subunit