Work

IL-4Rα Expression by Bone Marrow-Derived Cells Is Necessary and Sufficient for Host Protection against Acute Schistosomiasis

Year: 2008

Type: article

Abstract: 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.

Source: The Journal of Immunology

DOI: 10.4049/jimmunol.180.7.4948

Authors: De’Broski R Herbert, Tatyana Orekov, Charles Perkins, Marc E Rothenberg, Fred D Finkelman

Institutions: Cincinnati VA Medical Center, University of Cincinnati, Cincinnati Children's Hospital Medical Center

Language: English

Topic: Parasites and Host Interactions

Subfield: Parasitology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: U.S. Department of Veterans Affairs, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases