马内菲Talaromyces marneffei诱导的剂量依赖性M2巨噬细胞极化通过精氨酸-鸟氨酸周期激活促进肺癌细胞生长。

IF 5.5 3区 医学 Q1 IMMUNOLOGY
Anqi Chen, Qian Yu, Leliang Zheng, Junqi Yi, Ziying Tang, Huabo Ge, Yue Ning, Na Yin, Yaohuan Xie, Shengnan Chen, Wenhua Shi, Xiaoling She, Juanjuan Xiang, Jingqun Tang
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引用次数: 0

摘要

现在人们普遍认为肺里有各种各样的微生物。肺部微生物群的生态失调已被发现影响肺癌的进展。真菌是肺部微生物群的主要组成部分。然而,真菌群落或特定物种与肺癌之间的因果关系尚不清楚。为了解决这个问题,我们进行了一项研究,使用散弹枪宏基因组学检查非小细胞肺癌(NSCLC)患者肺部真菌群的组成。通过Wilcoxon秩和检验确定NSCLC患者和非癌症对照组之间的差异分类群。采用巢式PCR法测定特定真菌种类的丰度。通过代谢组学分析,研究了特定真菌在细胞内感染所引发的巨噬细胞代谢重编程。体外和体内实验研究了该真菌对肿瘤细胞生长的影响。结果表明,子囊菌门、微孢子虫门和粘菌门是肺部真菌的优势类群。马尔尼菲Talaromyces marneffei (T.marneffei)是肺癌患者与非癌症对照间差异最显著的真菌,其丰度与肺癌呈正相关。肺癌动物模型实验表明,马氏霉具有促进肺癌生长的作用。我们的研究还表明,T.marneffei通过精氨酸-鸟氨酸周期激活,诱导剂量依赖性M2巨噬细胞极化,从而促进肺癌细胞的生长。此外,抑制精氨酸酶可以降低巨噬细胞M2极化,降低巨噬细胞内T. marneffei的存活率。综上所述,我们的研究表明,肺中T. marneffei丰度的增加通过触发精氨酸诱导的巨噬细胞M2极化来影响肺癌细胞的生长。这些发现为开发针对巨噬细胞内真菌存活的治疗方法提供了潜在的药物靶点,以对抗癌症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dose-dependent M2 macrophage polarization induced by Talaromyces marneffei promotes lung cancer cell growth via arginine-ornithine-cycle activation.

It is now widely accepted that lungs are colonized by diverse microbes. Dysbiosis of the lung microbiota has been found to affect the progression of lung cancer. Fungi are a major component of the lung microbiota. However, the causal links between the mycobiome or specific species and lung cancer remain unclear. To address this, we conducted a study examining the composition of lung mycobiota in Non-Small-Cell Lung Cancer (NSCLC) patients using shotgun metagenomics. The differential taxa between NSCLC patients and non-cancer controls were defined by the Wilcoxon rank-sum test. Nested PCR was used to measure the abundance of specific fungal species. Metabolomics analysis was performed to investigate the metabolic reprogramming of macrophages triggered by intracellular infection of specific fungal species. In vitro and in vivo assays were conducted to examine the effect of the specific fungus on cancer cell growth. Our findings showed that Ascomycota, Microsporidia and Mucoromycota were the dominant fungal taxa in the lungs. Talaromyces marneffei (T.marneffei) was the most significantly differential fungus between lung cancer patients and non-cancer controls, with its abundance positively correlated with lung cancer. The lung cancer animal model demonstrated that T.marneffei promotes lung cancer growth. Our study also demonstrated that T.marneffei promotes lung cancer cell growth by inducing dose-dependent M2 macrophage polarization through arginine-ornithine-cycle activation. Furthermore, inhibition of arginase can reduce M2 polarization of macrophages and the survival of T. marneffei inside macrophages. In summary, our study reveals that the increased abundance of T. marneffei in the lungs affects lung cancer cell growth by triggering arginine-induced M2 polarization of macrophages. These findings provide potential drug targets for the development of therapies aimed at targeting the survival of fungi inside macrophages in the fight against cancer.

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来源期刊
CiteScore
10.60
自引率
0.00%
发文量
29
审稿时长
1 months
期刊介绍: Medical Microbiology and Immunology (MMIM) publishes key findings on all aspects of the interrelationship between infectious agents and the immune system of their hosts. The journal´s main focus is original research work on intrinsic, innate or adaptive immune responses to viral, bacterial, fungal and parasitic (protozoan and helminthic) infections and on the virulence of the respective infectious pathogens. MMIM covers basic, translational as well as clinical research in infectious diseases and infectious disease immunology. Basic research using cell cultures, organoid, and animal models are welcome, provided that the models have a clinical correlate and address a relevant medical question. The journal also considers manuscripts on the epidemiology of infectious diseases, including the emergence and epidemic spreading of pathogens and the development of resistance to anti-infective therapies, and on novel vaccines and other innovative measurements of prevention. The following categories of manuscripts will not be considered for publication in MMIM: submissions of preliminary work, of merely descriptive data sets without investigation of mechanisms or of limited global interest, manuscripts on existing or novel anti-infective compounds, which focus on pharmaceutical or pharmacological aspects of the drugs, manuscripts on existing or modified vaccines, unless they report on experimental or clinical efficacy studies or provide new immunological information on their mode of action, manuscripts on the diagnostics of infectious diseases, unless they offer a novel concept to solve a pending diagnostic problem, case reports or case series, unless they are embedded in a study that focuses on the anti-infectious immune response and/or on the virulence of a pathogen.
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