The CARDS toxin of Mycoplasma pneumoniae induces a positive feedback loop of type 1 immune response.
The CARDS toxin of Mycoplasma pneumoniae induces a positive feedback loop of type 1 immune response.
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肺炎支原体的CARDS毒素诱导1型免疫反应的正反馈循环
DOI：
10.3389/fimmu.2022.1054788
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
背景在过去的3-5年里，肺炎支原体已成为儿童社区获得性肺炎的主要病原体。对M.肺炎感染尚未完全阐明。方法蛋白质芯片研究显示，在M.肺炎感染。本研究以医院为基础，探讨1型免疫应答炎症因子干扰素（IFN）-γ和CXCL 9在M.肺炎（MPP）。然后，通过体外实验，探讨IFN-γ刺激F-DCs（与Flt 3L共同孵育的树突状细胞）是否促进Th 1细胞分化，以及IFN-γ诱导巨噬细胞分泌CXCL 9的途径和CXCL 9在促进Th 1细胞迁移中的作用。结果CXCL 9在发热高峰、发热持续时间> 7 d、影像学表现为叶性或节段性胸腔积液、合并胸腔积液的患者中表达上调（P<0.05）。患者外周血IFN-γ和CXCL 9水平均高于健康对照组，且两者呈正相关（r=0.502，P<0.05）。支气管肺泡灌洗液（BALF）中CXCL 9的表达水平明显高于外周血，且BALF中CXCL 9的表达水平高于健康对照组（均P<0.05）。我们的流式细胞术分析显示，M1-表型巨噬细胞（CD 16 + CD 64 + CD 163 −）在MPP患儿的BALF中占主导地位。在体外实验中，F-DCs经雷公藤毒素刺激后可促进CD 4 + IFN-γ+ Th（Th 1）细胞的分化（P<0.05）。此外，IFN-γ诱导M1型巨噬细胞中CXCL 9的高水平表达，并呈剂量依赖性和时间依赖性。转染STAT 1-siRNA-1的巨噬细胞下调CXCL 9的表达（P<0.05），CXCL 9促进Th 1细胞迁移（P<0.05）。结论巨噬细胞毒素诱导的1型免疫反应正反馈环。这种假定的机制可能是有用的，在未来的调查免疫干预方法，肺炎支原体感染。肺炎肺炎。
Background Within the past 3-5 years, Mycoplasma pneumoniae has become a major pathogen of community-acquired pneumonia in children. The pathogenic mechanisms involved in M. pneumoniae infection have not been fully elucidated. Methods Previous protein microarray studies have shown a differential expression of CXCL9 after M. pneumoniae infection. Here, we conducted a hospital-based study to explore the clinical significance of the type 1 immune response inflammatory factors interferon (IFN)-γ and CXCL9 in patients with M. pneumoniae pneumonia (MPP). Then, through in vitro experiments, we explored whether CARDS toxin stimulated F-DCs (dendritic cells incubated with Flt3L) to promote Th-cell differentiation; we also investigated the IFN-γ-induced CXCL9 secretion pathway in macrophages and the role of CXCL9 in promoting Th1 cell migration. Results The CXCL9 expression level was upregulated among patients with a higher fever peak, fever duration of greater than 7 days, an imaging manifestation of lobar or segmental, or combined pleural effusion (P<0.05). The peripheral blood levels of IFN-γ and CXCL9, which were higher in patients than in the healthy control group, were positively correlated with each other (r=0.502, P<0.05). In patients, the CXCL9 expression level was significantly higher in the bronchoalveolar lavage fluid (BALF) than in the peripheral blood, and the BALF CXCL9 expression level was higher than that in the healthy control group (all P<0.05). Our flow cytometry analysis revealed that M1-phenotype macrophages (CD16+ CD64+ CD163−) were predominant in the BALF from children with MPP. In in vitro experiments, F-DCs stimulated with CARDS toxin promoted the differentiation of CD4+ IFN-γ+ Th (Th1) cells (P<0.05). Moreover, IFN-γ induced high levels of CXCL9 expression in M1-type macrophages in a dose-dependent and time-dependent manner. Additionally, macrophages transfection with STAT1-siRNA-1 downregulated the expression of CXCL9 (P<0.05), and CXCL9 promoted Th1 cell migration (P<0.05). Conclusions Our findings suggest that CARDS toxin induces a type 1 immune response positive feedback loop during M. pneumoniae infection; this putative mechanism may be useful in future investigations of immune intervention approaches for M. pneumoniae pneumonia.
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影响因子：
6
作者：
Lo Sicco C;Reverberi D;Balbi C;Ulivi V;Principi E;Pascucci L;Becherini P;Bosco MC;Varesio L;Franzin C;Pozzobon M;Cancedda R;Tasso R
通讯作者：
Tasso R
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影响因子：
5.2
作者：
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影响因子：
3.9
作者：
Han HY;Park KC;Yang EA;Lee KY
通讯作者：
Lee KY
影响因子：
4.5
作者：
Biagi C;Cavallo A;Rocca A;Pierantoni L;Antonazzo D;Dondi A;Gabrielli L;Lazzarotto T;Lanari M
通讯作者：
Lanari M
影响因子：
3.8
作者：
Chung HL;Shin JY;Ju M;Kim WT;Kim SG
通讯作者：
Kim SG