Enhanced Proinflammatory Cytokine Production and Immunometabolic Impairment of NK Cells Exposed to Mycobacterium tuberculosis and Cigarette Smoke

Rao, Yafei; Gai, Xiaoyan; Le, Yanqing; Xiong, Jing; Liu, Yujia; Zhang, Xueyang; Wang, Jundong; Cao, Weipeng; Sun, Yongchang

doi:10.3389/fcimb.2021.799276

Cited by 5 publications

(5 citation statements)

References 39 publications

(55 reference statements)

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“…Our previous study showed that Mtb infection promoted cigarette smoke-exposed macrophages to polarise toward both M1 and M2 phenotypes, along with enhanced production of MMP9 and MMP12 27. In an earlier study, we reported increased cytokine production and impaired cell metabolism in natural killer cells after coexposure to cigarette smoke and purified protein derivative 29 30…”

Section: Discussionmentioning

confidence: 96%

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Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study

Gai,

Cao,

Rao

et al. 2023

BMJ Open

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IntroductionPost-tuberculosis lung damage (PTLD) refers to the residual pulmonary impairment following the completion of antituberculosis (TB) therapy, characterised by persistent respiratory symptoms and abnormal pulmonary function. The risk factors and biomarkers for PTLD have been scarcely investigated. More importantly, whether and to what extent cigarette smoking is involved in PTLD remain to be known.Methods and analysisThis prospective observational study will enrol 400 male smoking or non-smoking patients aged 25–65 years, with newly confirmed active TB between 2022 and 2024, from the Department of Respiratory and Critical Care Medicine at Peking University Third Hospital and the Tuberculosis Department at Beijing Geriatric Hospital. Because females rarely smoke in China, we will enrol only males in this study. Demographic data, smoking history and amount, clinical symptoms, lung function, and chest CT findings will be prospectively collected. Respiratory questionnaires, lung function measurements and chest CT examinations will be performed immediately after, and 1 year, 2 years and 3 years after the completion of TB treatment. Peripheral blood samples will be obtained at baseline and at the end of anti-TB therapy, and a Luminex xMAP-based multiplex immunoassay will be used to measure inflammatory mediators and cytokines in serum. The collected data will be analysed to determine the incidence and factors/biomarkers of PTLD according to smoking status.Ethics and disseminationThe study was approved by the Ethics Committee of Peking University Third Hospital (approval number: (2022)271-03; approval date: 8 June 2022). The research results will be disseminated through scientific and medical conferences and will be published in an academic journal.Trial registration numberNCT04966052.

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Section: Discussionmentioning

confidence: 96%

“… 27 In an earlier study, we reported increased cytokine production and impaired cell metabolism in natural killer cells after coexposure to cigarette smoke and purified protein derivative. 29 30 …”

Section: Discussionmentioning

confidence: 99%

Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study

Gai,

Cao,

Rao

et al. 2023

BMJ Open

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“… 49 Although the exact mechanism of defective response of NK cells remains unclear, at present, evidence indicates that MTB may hijack the host gene expression to inhibit the immuno-metabolic reprogramming of NK cells. 50 , 51 Importantly, this immunosuppressed status could not be reversed by cytokine-mediated activation. Further study is urgently required to elucidate the molecular mechanism involved in impaired IFN-γ production capability of NK cells in TB patients.…”

Section: Discussionmentioning

confidence: 99%

Attenuated Cytokine-Induced Memory-Like Natural Killer Cell Responses to Mycobacterium tuberculosis in Tuberculosis Patients

Chen¹,

Li²,

Yuan³

et al. 2023

IDR

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Purpose This study aimed to investigate the phenotype, proliferation and functional alterations of cytokine-induced memory-like natural killer (CIML NK) cells from healthy subjects and TB patients, and assessed the efficacy of CIML NK cells in response to H37Rv-infected U937 cells in vitro. Methods Fresh peripheral blood mononuclear cells (PBMCs) were isolated from healthy people and tuberculosis patients and activated for 16h using low-dose IL-15, or IL-12, IL-15, IL-18 combination or IL-12, IL-15, IL-18 and MTB H37Rv lysates, respectively, followed by low-dose IL-15 maintenance for another 7 days. Then, the PBMCs were co-cultured with K562 and H37Rv-infected U937, and the purified NK cells were co-cultured with H37Rv infected U937. The phenotype, proliferation and response function of CIML NK cells were assessed using flow cytometry. Finally, colony forming units were enumerated to confirm the survival of intracellular MTB. Results CIML NK phenotypes from TB patients were similar to healthy controls. CIML NK cells undergo higher rates of proliferation after IL-12/15/18 pre-activation. Moreover, the poor expansion potential of CIML NK cells co-stimulated with MTB lysates. CIML NK cells from healthy individuals showed enhanced IFN-γ functional to H37Rv infected U937 cells, along with significantly enhanced killing of H37Rv. However, the CIML NK cells from TB patients show attenuated IFN-γ production and now enhanced the ability of killing intracellular MTB compared to those from healthy donors after co-cultured with H37Rv infected U937. Conclusion CIML NK cells from healthy individuals exist the increased ability of IFN-γ secretion and boosted anti-MTB activity in vitro, which from TB patients show impaired IFN-γ production and no enhanced anti-MTB activity compared to those from healthy donors. Additionally, we observe the poor expansion potential of CIML NK cells co-stimulated with antigens from MTB. These results open up new possibilities for NK cell-based anti-tuberculosis immunotherapeutic strategies.

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“…NK cells are important innate immune effectors, and their abnormal activation can lead to tissue injury and chronic inflammation [48]. CS exposure may aggravate the injury of lung epithelial cells by increasing the cytotoxicity and cytokine production of NK cells [49]. Overall, the M2 macrophages and the activated NK cells play a pivotal role in airway inflammation and lung parenchyma destruction.…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of various RNA transcripts and construction of biological regulatory networks at the post-transcriptional level for chronic obstructive pulmonary disease

Li,

Zhang,

Dong

et al. 2023

J Transl Med

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Background Although chronic inflammation, oxidative stress, airway remodeling, and protease-antiprotease imbalance have been implicated in chronic obstructive pulmonary disease (COPD), the exact pathogenesis is still obscure. Gene transcription and post-transcriptional regulation have been taken into account as key regulators of COPD occurrence and development. Identifying the hub genes and constructing biological regulatory networks at the post-transcriptional level will help extend current knowledge on COPD pathogenesis and develop potential drugs. Methods All lung tissues from non-smokers (n = 6), smokers without COPD (smokers, n = 7), and smokers with COPD (COPD, n = 7) were collected to detect messenger RNA (mRNA), microRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) expression and identify the hub genes. Biological regulatory networks were constructed at the post-transcriptional level, including the RNA-binding protein (RBP)-hub gene interaction network and the competitive endogenous RNA (ceRNA) network. In addition, we assessed the composition and abundance of immune cells in COPD lung tissue and predicted potential therapeutic drugs for COPD. Finally, the hub genes were confirmed at both the RNA and protein levels. Results Among the 20 participants, a total of 121169 mRNA transcripts, 1871 miRNA transcripts, 4244 circRNA transcripts, and 122130 lncRNA transcripts were detected. There were differences in the expression of 1561 mRNAs, 48 miRNAs, 33 circRNAs, and 545 lncRNAs between smokers and non-smokers, as well as 1289 mRNAs, 69 miRNAs, 32 circRNAs, and 433 lncRNAs between smokers and COPD patients. 18 hub genes were identified in COPD. TGF-β signaling and Wnt/β-catenin signaling may be involved in the development of COPD. Furthermore, the circRNA/lncRNA-miRNA-mRNA ceRNA networks and the RBP-hub gene interaction network were also constructed. Analysis of the immune cell infiltration level revealed that M2 macrophages and activated NK cells were increased in COPD lung tissues. Finally, we identified that the ITK inhibitor and oxybutynin chloride may be effective in treating COPD. Conclusions We identified several novel hub genes involved in COPD pathogenesis. TGF-β signaling and Wnt/β-catenin signaling were the most dysregulated pathways in COPD patients. Our study constructed post-transcriptional biological regulatory networks and predicted small-molecule drugs for the treatment of COPD, which enhanced the existing understanding of COPD pathogenesis and suggested an innovative direction for the therapeutic intervention of the disease.

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Enhanced Proinflammatory Cytokine Production and Immunometabolic Impairment of NK Cells Exposed to Mycobacterium tuberculosis and Cigarette Smoke

Cited by 5 publications

References 39 publications

Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study

Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study

Attenuated Cytokine-Induced Memory-Like Natural Killer Cell Responses to Mycobacterium tuberculosis in Tuberculosis Patients

Systematic analysis of various RNA transcripts and construction of biological regulatory networks at the post-transcriptional level for chronic obstructive pulmonary disease

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