Streptococcus pneumoniae PepO promotes host anti-infection defense via autophagy in a Toll-like receptor 2/4 dependent manner
Streptococcus pneumoniae PepO promotes host anti-infection defense via autophagy in a Toll-like receptor 2/4 dependent manner
复制标题
肺炎链球菌PepO通过Toll样受体2/4依赖性方式自噬促进宿主抗感染防御
DOI：
10.1080/21505594.2020.1739411
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发表时间：
2020-01
期刊：
影响因子：
5.2
通讯作者：
Xuemei Zhang
中科院分区：
文献类型：
--
作者：
Zhaoche Shu;Jun Yuan;Hong Wang;Jinghui Zhang;Sijie Li;Hong Zhang;Yusi Liu;Yibing Yin;Xuemei Zhang
摘要巨噬细胞直接清除入侵的微生物，引发一系列免疫反应，是宿主抗菌防御所必需的。在这里，我们鉴定了肺炎链球菌蛋白Pepo，作为TLR2/TLR4的双配体。我们发现，Pepo增强了巨噬细胞的非特异性吞噬和杀菌活性，这与诱导巨噬细胞自噬有关，因为抑制自噬显著降低了Pepo处理的巨噬细胞的吞噬和杀菌活性。我们证实，PEPO的这些作用依赖于与TLR2和TLR4的相互作用。TLR2或TLR4缺乏部分消除了PEPO的作用，而TLR2/TLR4缺乏则完全消除了PEPO的作用。体内研究表明，PEPO可显著降低WT小鼠的细菌载量，而巨噬细胞的耗竭或TLR2/TLR4缺乏可使PEPO的作用消失。我们的研究结果提示了PEPO的治疗潜力，并为免疫治疗感染性疾病提供了实验依据。
ABSTRACT Macrophage is essential for host anti-bacterial defense by directly eliminating invading microbes and inducing a series of immune reactions. Here we identified a Streptococcus pneumoniae protein, PepO, as a TLR2/TLR4 bi-ligand. We found that PepO enhances macrophage unspecific phagocytosis and bactericidal activity, which is related to the induction of autophagy in macrophage, for the inhibition of autophagy significantly decreased the phagocytosis and bactericidal activity of PepO-treated macrophage. We confirmed that these effects of PepO are dependent on interacting with both TLR2 and TLR4. The tlr2 or tlr4 deficiency partially abolished the effect of PepO while tlr2/tlr4 deficiency abolished it completely. In vivo study demonstrated that PepO reduced the bacteria load in WT mice significantly, while the depletion of macrophage or tlr2/tlr4 deficiency abrogated the effect of PepO. Our findings suggested the therapeutic potential of PepO and provided experimental evidence for immunotherapy against infectious disease.
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DOI：
10.1073/pnas.042355399
发表时间：
2002-02-19
影响因子：
11.1
作者：
Rassa, JC;Meyers, JL;Ross, SR
通讯作者：
Ross, SR
影响因子：
1.8
作者：
Abdul-Cader, Mohamed Sarjoon;De Silva Senapathi, Upasama;Abdul-Careem, Mohamed Faizal
通讯作者：
Abdul-Careem, Mohamed Faizal
影响因子：
3.1
作者：
Wu, Kaifeng;Zhang, Xuemei;Yin, Yibing
通讯作者：
Yin, Yibing
影响因子：
7.3
作者：
Bah A;Vergne I
通讯作者：
Vergne I
影响因子：
8.9
作者：
Nakamura, T;Abu-Dahab, R;Schäfers, HJ
通讯作者：
Schäfers, HJ