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.

中文翻译：

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肺炎链球菌PepO以Toll样受体2/4依赖性方式通过自噬促进宿主抗感染防御。

巨噬细胞通过直接消除入侵的微生物并诱导一系列免疫反应，对宿主的抗菌防御至关重要。在这里，我们确定了肺炎链球菌蛋白PepO为TLR2 / TLR4双配体。我们发现PepO增强巨噬细胞的非特异性吞噬作用和杀菌活性，这与巨噬细胞自噬的诱导有关，因为抑制自噬作用显着降低了PepO处理的巨噬细胞的吞噬作用和杀菌活性。我们证实，PepO的这些作用取决于与TLR2和TLR4的相互作用。tlr2或tlr4缺乏症部分消除了PepO的作用，而tlr2 / tlr4缺乏症则完全消除了PepO的作用。体内研究表明，PepO可显着降低野生型小鼠的细菌载量，而巨噬细胞的消耗或tlr2 / tlr4缺乏则废除了PepO的作用。我们的发现提示了PepO的治疗潜力，并为针对传染病的免疫疗法提供了实验证据。