Integrated analysis of microbiome and host transcriptome unveils correlations between lung microbiota and host immunity in bronchoalveolar lavage fluid of pneumocystis pneumonia patients.

IF 2.6 4区医学 Q3 IMMUNOLOGY Microbes and Infection Pub Date : 2024-06-06 DOI:10.1016/j.micinf.2024.105374

Ling Zhang, Miaotian Cai, Xin Zhang, Sitong Wang, Lijun Pang, Xue Chen, Caopei Zheng, Yuqing Sun, Ying Liang, Shan Guo, Feili Wei, Yulin Zhang

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Abstract

Objective: The lung microbiota of patients with pulmonary diseases is disrupted and impacts the immunity. The microbiological and immune landscape of the lungs in patients with pneumocystis pneumonia (PCP) remains poorly understood.

Methods: Multi-omics analysis and machine learning were performed on bronchoalveolar lavage fluid to explore interaction between the lung microbiota and host immunity in PCP. Then we constructed a diagnostic model using differential genes with LASSO regression and validated by qPCR. The immune infiltration analysis was performed to explore the landscape of lung immunity in patients with PCP.

Results: Patients with PCP showed a low alpha diversity of lung microbiota, accompanied by the elevated abundance of Firmicutes, and the differential expressed genes (DEGs) analysis displayed a downregulation of MAPK signaling. The MAPK10, TGFB1, and EFNA3 indicated a potential to predict PCP (AUC = 0.86). The lung immune landscape in PCP showed the lower levels of naïve CD4⁺ T cells and activated dendritic cells. The correlation analysis of the MAPK signaling pathway-related DEGs and the differential microorganisms at the level of phylum showed that the Firmicutes was negatively correlated with these DEGs.

Conclusion: We profiled the characteristics of lung microbiota and immune landscape in PCP, which may contribute to elucidating the mechanism of PCP.

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对微生物组和宿主转录组的综合分析揭示了肺孢子菌肺炎患者支气管肺泡灌洗液中肺微生物组与宿主免疫之间的相关性。

目的：肺部疾病患者的肺部微生物群遭到破坏并影响免疫力。人们对肺孢子菌肺炎（PCP）患者肺部的微生物和免疫状况仍然知之甚少：方法：我们对支气管肺泡灌洗液进行了多组学分析和机器学习，以探索肺孢子菌肺炎患者肺部微生物群与宿主免疫之间的相互作用。然后，我们利用 LASSO 回归法构建了一个差异基因诊断模型，并通过 qPCR 进行了验证。我们还进行了免疫浸润分析，以探索五氯苯酚患者的肺部免疫状况：结果：五氯苯酚患者的肺部微生物群的α多样性较低，伴随着真菌丰度的升高，差异表达基因（DEGs）分析显示了MAPK信号的下调。MAPK10、TGFB1和EFNA3显示出预测PCP的潜力（AUC = 0.86）。PCP 患者的肺部免疫状况显示，幼稚 CD4+ T 细胞和活化树突状细胞水平较低。MAPK信号通路相关的DEGs与不同微生物门的相关性分析表明，真菌与这些DEGs呈负相关：我们分析了五氯苯酚肺微生物群和免疫景观的特征，这可能有助于阐明五氯苯酚的发病机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microbes and Infection 医学-病毒学

CiteScore

12.60

自引率

1.70%

发文量

审稿时长

40 days

期刊介绍： Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular: the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms. the immune response to infection, including pathogenesis and host susceptibility. emerging human infectious diseases. systems immunology. molecular epidemiology/genetics of host pathogen interactions. microbiota and host "interactions". vaccine development, including novel strategies and adjuvants. Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal. Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.