Commensal microbiota maintains alveolar macrophages with a low level of CCL24 production to generate anti-metastatic tumor activity.
Commensal microbiota maintains alveolar macrophages with a low level of CCL24 production to generate anti-metastatic tumor activity.
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共生微生物群维持肺泡巨噬细胞产生低水平的 CCL24，从而产生抗转移肿瘤活性
DOI：
10.1038/s41598-017-08264-8
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发表时间：
2017-08-07
影响因子：
4.6
通讯作者：
Hu S
中科院分区：
文献类型：
--
作者：
Cheng M;Chen Y;Wang L;Chen W;Yang L;Shen G;Xu T;Shen G;Tian Z;Hu S
微生物群维持宿主组织稳态并影响组织驻留的巨噬细胞。然而，肺泡细菌调节肺泡巨噬细胞的机制尚不清楚。在这里，通过使用抗生素治疗的（Abt）小鼠模型，我们发现肺泡细菌耗竭诱导肺泡巨噬细胞的频率和数量降低。这种效应伴随着参与几种生物学途径的基因水平的改变，包括M2巨噬细胞极化，如通过基因表达分析所确定的。Abt小鼠肺泡巨噬细胞Arg 1、CCL 24、IL-13、IL-10、IL-6和IL-1β的蛋白和基因水平较高，通过重组Abt小鼠上呼吸道细菌，这些蛋白和基因水平可以恢复到正常水平。此外，肺泡巨噬细胞执行显着增强M2功能，特别是CCL 24分泌，在Abt小鼠攻击B16/F10黑色素瘤。正常肺泡巨噬细胞的连续转移或CCL 24的抗体中和显著恢复了γδT17细胞的减少并挽救了Abt小鼠的缺陷抗肿瘤反应，表明肺泡巨噬细胞来源的CCL 24的量的升高抑制了γδT细胞介导的抗肿瘤反应。总之，我们证明了肺泡细菌维持肺泡巨噬细胞产生低水平CCL 24的能力，这是肺中正常抗肿瘤反应所必需的。
Microbiota maintains host tissue homeostasis and influences tissue-resident macrophages. However, the mechanisms by which commensal bacteria in regulating the alveolar macrophages remain unclear. Here, by using an antibiotic-treated (Abt) mouse model, we found commensal bacteria depletion induced lower frequencies and numbers of alveolar macrophages. This effect was accompanied by the altered levels of genes involved in several biological pathways, including M2 macrophage polarization, as determined by gene expression analysis. Alveolar macrophages from the Abt mice had higher protein and gene levels of Arg1, CCL24, IL-13, IL-10, IL-6 and IL-1β, which could be recovered to normal levels by reconstructing commensal bacteria in the upper respiratory of Abt mice. Moreover, alveolar macrophages performed significant enhancement of M2 functions, especially CCL24 secretion, in the Abt mice challenged with B16/F10 melanoma. Adoptive transfer of normal alveolar macrophages or antibody neutralization of CCL24 significantly recovered the decrease of γδT17 cells and rescued the defect anti-tumor response of Abt mice, indicating the elevated amount of alveolar macrophage-derived CCL24 inhibited γδT cell mediated anti-tumor response. In conclusion, we demonstrated the ability of commensal bacteria to maintain alveolar macrophages with a low level of CCL24 production, which was necessary for the normal anti-tumor response in the lung.
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影响因子：
30.3
作者：
Benson A;Pifer R;Behrendt CL;Hooper LV;Yarovinsky F
通讯作者：
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DOI：
10.1073/pnas.1019378108
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DOI：
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影响因子：
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