期刊
INFECTION AND IMMUNITY
卷 84, 期 12, 页码 3471-3483出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00681-16
关键词
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资金
- Eyes High University of Calgary
- Brazilian Post-doctoral Fellowship Ciencias Sem Fronteiras CNPq
- Alberta Innovates - Health Solutions (AIHS)
- Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (NSERC)
- Gouvernement du Canada | Canadian Institutes of Health Research (CIHR)
- Canadian Association of Gastroenterology (CAG)
- Alberta Innovates [201500767] Funding Source: researchfish
Awareness of the immunological underpinnings of host-parasite interactions may reveal immune signaling pathways that could be used to treat inflammatory disease in humans. Previously we showed that infection with the rat tapeworm, Hymenolepis diminuta, used as a model helminth, or systemic delivery of worm antigen (HdAg) significantly reduced the severity of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice. Extending these analyses, intraperitoneal injection of HdAg dosedependently suppressed dextran sodium sulfate (DSS)-induced colitis, and this was paralleled by reduced gamma interferon (IFN-gamma), interleukin-17 (IL-17), and tumor necrosis factor alpha (TNF-alpha) production and increased IL-10 production from mitogen- activated splenocytes. Treatment with HdAg resulted in a CCR2-dependent recruitment of CDllb(+) F4/80(+) Ly6C(hi) Gr-1(lo) monocyte-like cells into the peritoneum 24 h later that were predominantly programmed death ligand 1 (PD-L1) positive and CXCR2 negative. In vitro assays indicated that these cells were unable to suppress T cell proliferation but enhanced IL-10 and IL-4 production from activated T cells. Adoptive transfer of the HdAg-recruited monocytic cells into naive mice blocked DSSinduced colitis. These findings add to the variety of means by which treatment with parasitic helminth-derived antigens can ameliorate concomitant disease. A precise understanding of the mechanism(s) of action of HdAg and other helminth-derived antigens (and a parallel consideration of putative side effects) may lead to the development of novel therapies for human idiopathic disorders such as inflammatory bowel disease.
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