Journal article
Arginase I Suppresses IL-12/IL-23p40-Driven Intestinal Inflammation during Acute Schistosomiasis
The Journal of immunology (1950), v 184(11), pp 6438-6446
01 Jun 2010
PMID: 20483789
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Alternatively activated macrophages prevent lethal intestinal pathology caused by worm ova in mice infected with the human parasite Schistosoma mansoni through mechanisms that are currently unclear. This study demonstrates that arginase I (Arg I), a major product of IL-4- and IL-13-induced alternatively activated macrophages, prevents cachexia, neutrophilia, and endotoxemia during acute schistosomiasis. Specifically, Arg I-positive macrophages promote TGF-beta production and Foxp3 expression, suppress Ag-specific T cell proliferation, and limit Th17 differentiation. S. mansoni-infected Arg I-deficient bone marrow chimeras develop a marked accumulation of worm ova within the ileum but impaired fecal egg excretion compared with infected wild-type bone marrow chimeras. Worm ova accumulation in the intestines of Arg I-deficient bone marrow chimeras was associated with intestinal hemorrhage and production of molecules associated with classical macrophage activation (increased production of IL-6, NO, and IL-12/IL-23p40), but whereas inhibition of NO synthase-2 has marginal effects, IL-12/IL-23p40 neutralization abrogates both cachexia and intestinal inflammation and reduces the number of ova within the gut. Thus, macrophage-derived Arg I protects hosts against excessive tissue injury caused by worm eggs during acute schistosomiasis by suppressing IL-12/IL-23p40 production and maintaining the Treg/Th17 balance within the intestinal mucosa. The Journal of Immunology, 2010, 184: 6438-6446.
Metrics
Details
- Title
- Arginase I Suppresses IL-12/IL-23p40-Driven Intestinal Inflammation during Acute Schistosomiasis
- Creators
- De'Broski R. Herbert - College Station Medical CenterTatyana Orekov - United States Department of Veterans AffairsAmanda Roloson - United States Department of Veterans AffairsMonica Ilies - Drexel University, ChemistryCharles Perkins - United States Department of Veterans AffairsWilliam O'Brien - Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USAStephen Cederbaum - Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA 90095 USADavid W. Christianson - University of PennsylvaniaNives Zimmermann - College Station Medical CenterMarc E. Rothenberg - College Station Medical CenterFred D. Finkelman - Cincinnati Children's Hospital Medical Center
- Publication Details
- The Journal of immunology (1950), v 184(11), pp 6438-6446
- Publisher
- Amer Assoc Immunologists
- Number of pages
- 9
- Grant note
- U.S. Department of Veterans Affairs; US Department of Veterans Affairs RO1GM083204 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM083204 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemistry
- Web of Science ID
- WOS:000278439600059
- Scopus ID
- 2-s2.0-77953446979
- Other Identifier
- 991021903707104721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology