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IL-17-producing ?? T cells protect against Clostridium difficile infection.

ABSTRACT: Colitis caused by Clostridium difficile infection is a growing cause of human morbidity and mortality, especially after antibiotic use in health care settings. The natural immunity of newborn infants and protective host immune mediators against C. difficile infection are not fully understood, with data suggesting that inflammation can be either protective or pathogenic. Here, we show an essential role for IL-17A produced by ?? T cells in host defense against C. difficile infection. Fecal extracts from children with C. difficile infection showed increased IL-17A and T cell receptor ? chain expression, and IL-17 production by intestinal ?? T cells was efficiently induced after infection in mice. C. difficile-induced tissue inflammation and mortality were markedly increased in mice deficient in IL-17A or ?? T cells. Neonatal mice, with naturally expanded ROR?t+ ?? T cells poised for IL-17 production were resistant to C. difficile infection, whereas elimination of ?? T cells or IL-17A each efficiently overturned neonatal resistance against infection. These results reveal an expanded role for IL-17-producing ?? T cells in neonatal host defense against infection and provide a mechanistic explanation for the clinically observed resistance of infants to C. difficile colitis.

SUBMITTER: Chen YS

PROVIDER: S-EPMC7190913 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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IL-17-producing γδ T cells protect against Clostridium difficile infection.

Chen Yee-Shiuan YS Chen Iuan-Bor IB Pham Giang G Shao Tzu-Yu TY Bangar Hansraj H Way Sing Sing SS Haslam David B DB

The Journal of clinical investigation 20200501 5

Colitis caused by Clostridium difficile infection is a growing cause of human morbidity and mortality, especially after antibiotic use in health care settings. The natural immunity of newborn infants and protective host immune mediators against C. difficile infection are not fully understood, with data suggesting that inflammation can be either protective or pathogenic. Here, we show an essential role for IL-17A produced by γδ T cells in host defense against C. difficile infection. Fecal extract ...[more]

PMID: 31990686

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Project description:BackgroundVision loss in patients with wet/exudative age-related macular degeneration (AMD) is associated with choroidal neovascularization (CNV), and AMD is the leading cause of irreversible vision impairment in older adults. Interleukin-17A (IL-17A) is a component of the microenvironment associated with some autoimmune diseases. Previous studies have indicated that wet AMD patients have elevated serum IL-17A levels. However, the effect of IL-17A on AMD progression needs to be better understood. We aimed to investigate the role of IL-17A in a laser-induced CNV mouse model.MethodsWe established a laser-induced CNV mouse model in wild-type (WT) and IL-17A-deficient mice and then evaluated the disease severity of these mice by using fluorescence angiography. We performed enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) to analyze the levels of IL-17A and to investigate the immune cell populations in the eyes of WT and IL-17A-deficient mice. We used ARPE-19 cells to clarify the effect of IL-17A under oxidative stress.ResultsIn the laser-induced CNV model, the CNV lesions were larger in IL-17A-deficient mice than in WT mice. The numbers of γδ T cells, CD3+CD4+RORγt+ T cells, Treg cells, and neutrophils were decreased and the number of macrophages was increased in the eyes of IL-17A-deficient mice compared with WT mice. In WT mice, IL-17A-producing γδ T-cell numbers increased in a time-dependent manner from day 7 to 28 after laser injury. IL-6 levels increased and IL-10, IL-24, IL-17F, and GM-CSF levels decreased in the eyes of IL-17A-deficient mice after laser injury. In vitro, IL-17A inhibited apoptosis and induced the expression of the antioxidant protein HO-1 in ARPE-19 cells under oxidative stress conditions. IL-17A facilitated the repair of oxidative stress-induced barrier dysfunction in ARPE-19 cells.ConclusionsOur findings provide new insight into the protective effect of IL-17A in a laser-induced CNV model and reveal a novel regulatory role of IL-17A-producing γδ T cells in the ocular microenvironment in wet AMD.

Dataset Information

IL-17-producing ?? T cells protect against Clostridium difficile infection.

Publications

IL-17-producing γδ T cells protect against Clostridium difficile infection.

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