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首页> 外文期刊>Infection and immunity >Defect of CARD9 Leads to Impaired Accumulation of Gamma Interferon-Producing Memory Phenotype T Cells in Lungs and Increased Susceptibility to Pulmonary Infection with Cryptococcus neoformans
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Defect of CARD9 Leads to Impaired Accumulation of Gamma Interferon-Producing Memory Phenotype T Cells in Lungs and Increased Susceptibility to Pulmonary Infection with Cryptococcus neoformans

机译：CARD9的缺陷导致肺中产生γ干扰素的记忆表型T细胞的积累受损，并且对新型隐球菌的肺部感染易感性增加

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Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule signal that is critical for NF-κB activation and is triggered through C-type lectin receptors (CLRs), which are pattern recognition receptors that recognize carbohydrate structures. Previous studies have reported that Cryptococcus neoformans, a fungal pathogen that causes meningoencephalitis in AIDS patients, is recognized through some CLRs, such as mannose receptors or DC-SIGN. However, the role of CARD9 in the host defense against cryptococcal infection remains to be elucidated. In the present study, we analyzed the role of CARD9 in the host defense against pulmonary infection with C. neoformans. CARD9 gene-disrupted (knockout [KO]) mice were highly susceptible to this infection, as shown by the reduced fungal clearance in the infected lungs of CARD9 KO mice, compared to that in wild-type (WT) mice. Gamma interferon (IFN-γ) production was strongly reduced in CARD9 KO mice during the innate-immunity phase of infection. Reduced IFN-γ synthesis was due to impaired accumulation of NK and memory phenotype T cells, which are major sources of IFN-γ innate-immunity-phase production; a reduction in the accumulation of these cells was correlated with reduced CCL4, CCL5, CXCL9, and CXCL10 synthesis. However, differentiation of Th17 cells, but not of Th1 cells, was impaired at the adaptive-immunity phase in CARD9 KO mice compared to WT mice, although there was no significant difference in the infection susceptibility between interleukin 17A (IL-17A) KO and WT mice. These results suggest that CARD9 KO mice are susceptible to C. neoformans infection probably due to the reduced accumulation of IFN-γ-expressing NK and memory phenotype T cells at the early stage of infection.
机译：含有胱天蛋白酶募集结构域的蛋白质9（CARD9）是一个适配器分子信号，对于NF-κB激活至关重要，并通过C型凝集素受体（CLR）触发，C型凝集素受体是识别碳水化合物结构的模式识别受体。先前的研究报道，新隐球菌是一种真菌病原体，可在AIDS患者中引起脑膜脑炎，可通过某些CLR（如甘露糖受体或DC-SIGN）识别。但是，CARD9在宿主对抗隐球菌感染的防御中的作用仍有待阐明。在本研究中，我们分析了CARD9在宿主抵抗新孢梭菌肺部感染的防御中的作用。与野生型（WT）小鼠相比，受CARD9 KO小鼠感染的肺部真菌清除率降低表明，受CARD9基因破坏（敲除[KO]）的小鼠对这种感染高度敏感。在感染的先天免疫阶段，CARD9 KO小鼠的γ干扰素（IFN-γ）产生大大降低。 IFN-γ合成减少是由于NK和记忆表型T细胞积累受损，这是IFN-γ先天免疫阶段产生的主要来源。这些细胞积累的减少与CCL4，CCL5，CXCL9和CXCL10合成的减少有关。然而，与WT小鼠相比，在CARD9 KO小鼠的适应性免疫阶段，Th17细胞而非Th1细胞的分化受到了损害，尽管白介素17A（IL-17A）KO与白介素17A（IL-17A）KO之间的感染敏感性没有显着差异。 WT小鼠。这些结果表明，CARD9 KO小鼠很容易感染新孢子虫，这可能是由于感染初期表达IFN-γ的NK和记忆表型T细胞的积累减少所致。

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