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首页> 外文期刊>Infection and immunity >Dectin-1-Dependent Interleukin-22 Contributes to Early Innate Lung Defense against Aspergillus fumigatus
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Dectin-1-Dependent Interleukin-22 Contributes to Early Innate Lung Defense against Aspergillus fumigatus

机译：Dectin-1依赖白介素22有助于早期对抗烟曲霉的先天性肺部防御。

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We have previously reported that mice deficient in the beta-glucan receptor Dectin-1 displayed increased susceptibility to Aspergillus fumigatus lung infection in the presence of lower interleukin 23 (IL-23) and IL-17A production in the lungs and have reported a role for IL-17A in lung defense. As IL-23 is also thought to control the production of IL-22, we examined the role of Dectin-1 in IL-22 production, as well as the role of IL-22 in innate host defense against A. fumigatus. Here, we show that Dectin-1-deficient mice demonstrated significantly reduced levels of IL-22 in the lungs early after A. fumigatus challenge. Culturing cells from enzymatic lung digests ex vivo further demonstrated Dectin-1-dependent IL-22 production. IL-22 production was additionally found to be independent of IL-1β, IL-6, or IL-18 but required IL-23. The addition of recombinant IL-23 augmented IL-22 production in wild-type (WT) lung cells and rescued IL-22 production by lung cells from Dectin-1-deficient mice. In vivo neutralization of IL-22 in the lungs of WT mice resulted in impaired A. fumigatus lung clearance. Moreover, mice deficient in IL-22 also demonstrated a higher lung fungal burden after A. fumigatus challenge in the presence of impaired IL-1α, tumor necrosis factor alpha (TNF-α), CCL3/MIP-1α, and CCL4/MIP-1β production and lower neutrophil recruitment, yet intact IL-17A production. We further show that lung lavage fluid collected from both A. fumigatus-challenged Dectin-1-deficient and IL-22-deficient mice had compromised anti-fungal activity against A. fumigatus in vitro. Although lipocalin 2 production was observed to be Dectin-1 and IL-22 dependent, lipocalin 2-deficient mice did not demonstrate impaired A. fumigatus clearance. Moreover, lung S100a8, S100a9, and Reg3g mRNA expression was not lower in either Dectin-1-deficient or IL-22-deficient mice. Collectively, our results indicate that early innate lung defense against A. fumigatus is mediated by Dectin-1-dependent IL-22 production.
机译：我们以前曾报道过，在存在较低的白介素23（IL-23）和IL-17A的情况下，缺乏β-葡聚糖受体Dectin-1的小鼠对烟曲霉的肺部感染表现出更高的敏感性，并报道了这种作用IL-17A在肺部防御中。由于还认为IL-23可以控制IL-22的产生，因此我们检查了Dectin-1在IL-22产生中的作用，以及IL-22在针对烟曲霉的先天宿主防御中的作用。在这里，我们表明，烟曲霉攻击后早期，Dectin-1缺陷小鼠表现出明显降低的肺中IL-22水平。体外酶消化消化细胞进一步证明了Dectin-1依赖性IL-22的产生。另外发现IL-22的产生独立于IL-1β，IL-6或IL-18，但需要IL-23。重组IL-23的添加增加了野生型（WT）肺细胞中IL-22的产生，并挽救了Dectin-1缺陷小鼠肺细胞的IL-22产生。野生型小鼠肺中IL-22的体内中和作用导致烟曲霉肺部清除受损。此外，在存在受损的IL-1α，肿瘤坏死因子α（TNF-α），CCL3 /MIP-1α和CCL4 / MIP-的情况下，烟曲霉攻击后缺乏IL-22的小鼠也表现出较高的肺真菌负荷。 1β产生和中性粒细胞募集较低，但IL-17A产生完整。我们进一步显示，从烟曲霉菌挑战的Dectin-1缺陷小鼠和IL-22缺陷小鼠收集的肺灌洗液已损害了针对烟曲霉菌的体外抗真菌活性。尽管观察到lipocalin 2的产生是Dectin-1和IL-22依赖性的，但lipocalin 2缺陷的小鼠并未表现出烟曲霉清除率受损。此外，在Dectin-1缺陷型或IL-22缺陷型小鼠中，肺 S100a8 ， S100a9 和 Reg3g mRNA的表达均不降低。总的来说，我们的结果表明，针对烟曲霉的早期先天性肺防御是由依赖Dectin-1的IL-22产生的。

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