Cytadherence of Mycoplasma pneumoniae Induces Inflammatory Responses through Autophagy and Toll-Like Receptor 4
Cytadherence of Mycoplasma pneumoniae Induces Inflammatory Responses through Autophagy and Toll-Like Receptor 4
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DOI：
10.1128/iai.01961-14
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发表时间：
2014-07-01
影响因子：
3.1
通讯作者：
Watarai, Masahisa
中科院分区：
文献类型：
--
作者：
Shimizu, Takashi;Kimura, Yui;Watarai, Masahisa
肺炎支原体引起人类肺炎、气管支气管炎、咽炎和哮喘。肺炎支原体感染的发病机制归因于过度的免疫反应。我们之前证明肺炎支原体脂蛋白通过 Toll 样受体 2 (TLR2) 诱导炎症反应。在本研究中，我们证明肺炎支原体在 TLR2 敲除 (KO) 小鼠的巨噬细胞中诱导强烈的炎症反应。与野生型（WT）小鼠的巨噬细胞相比，TLR2 KO巨噬细胞的细胞因子产生增加。热灭活、抗生素处理和过度生长的肺炎支原体未能诱导 TLR2 KO 巨噬细胞的炎症反应。 3-甲基腺嘌呤和氯喹是自噬抑制剂，可减少 TLR2 KO 巨噬细胞炎症反应的诱导。在用 TLR4 抑制剂 VIPER 处理的巨噬细胞以及从 TLR2 和 TLR4 (TLR2/4) 双 KO 小鼠获得的巨噬细胞中，这些炎症反应也受到抑制。通过转座子诱变获得了两个缺乏诱导 TLR2 KO 巨噬细胞炎症反应能力的突变体。将转座子插入编码 ATP 合酶 F0F1 epsilon 亚基的 atpC 和编码假设蛋白 MPN333 的 F10_orf750 中。这些突变体表现出细胞粘附的缺陷。这些结果表明肺炎支原体的细胞粘附通过 TLR4 和自噬诱导炎症反应。
Mycoplasma pneumoniae causes pneumonia, tracheobronchitis, pharyngitis, and asthma in humans. The pathogenesis of M. pneumoniae infection is attributed to excessive immune responses. We previously demonstrated that M. pneumoniae lipoproteins induced inflammatory responses through Toll-like receptor 2 (TLR2). In the present study, we demonstrated that M. pneumoniae induced strong inflammatory responses in macrophages derived from TLR2 knockout (KO) mice. Cytokine production in TLR2 KO macrophages was increased compared with that in the macrophages of wild-type (WT) mice. Heat-killed, antibiotic-treated, and overgrown M. pneumoniae failed to induce inflammatory responses in TLR2 KO macrophages. 3-Methyladenine and chloroquine, inhibitors of autophagy, decreased the induction of inflammatory responses in TLR2 KO macrophages. These inflammatory responses were also inhibited in macrophages treated with the TLR4 inhibitor VIPER and those obtained from TLR2 and TLR4 (TLR2/4) double-KO mice. Two mutants that lacked the ability to induce inflammatory responses in TLR2 KO macrophages were obtained by transposon mutagenesis. The transposons were inserted in atpC encoding an ATP synthase F0F1 epsilon subunit and F10_orf750 encoding hypothetical protein MPN333. These mutants showed deficiencies in cytadherence. These results suggest that cytadherence of M. pneumoniae induces inflammatory responses through TLR4 and autophagy.