Infection of Mycobacterium tuberculosis Promotes Both M1/M2 Polarization and MMP Production in Cigarette Smoke-Exposed Macrophages

Le, Yanqing; Cao, Weipeng; Zhou, Lu; Fan, Xueli; Liu, Qiangui; Liu, Fusheng; Gai, Xiaoyan; Chang, Chun; Xiong, Jing; Rao, Yafei; Li, Aling; Xu, Wei; Liu, Beibei; Wang, Tong; Wang, Beinan; Sun, Yongchang

doi:10.3389/fimmu.2020.01902

Cited by 46 publications

(39 citation statements)

References 47 publications

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“… 28 , 37 A growing body of evidence indicates that M2 macrophages can secrete MMP9 and MMP12. 38 , 39 However, the relationship between macrophage polarization and MMPs production is complex and remains controversial. Macrophages can be polarized in one of two directions.…”

Section: Discussionmentioning

confidence: 99%

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

Liu¹,

Zhang²,

Yang³

et al. 2022

COPD

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Background Macrophage polarization plays an important role in the pathogenesis of COPD emphysema. Changes in macrophage polarization in COPD remain unclear, while polarization and ferroptosis are essential factors in its pathogenesis. Therefore, this study investigated the relationship between macrophage polarization and ferroptosis in COPD emphysema. Methods We measured macrophage polarization and the levels of matrix metalloproteinases (MMPs) in the lung tissues of COPD patients and cigarette smoke (CS)-exposed mice. Flow cytometry was used to determine macrophage (THP-M cell) polarization changes. Ferroptosis was examined by FerroOrange, Perls’ DAB, C11-BODIPY and 4-HNE staining. Nuclear receptor coactivator 4 (NCOA4) was measured in the lung tissues of COPD patients and CS-exposed mice by western blotting. A cell study was performed to confirm the regulatory effect of NCOA4 on macrophage polarization. Results Increased M2 macrophages and MMP9 and MMP12 levels were observed in COPD patients, CS-exposed mice and THP-M cells cocultured with CS extract (CSE)-treated human bronchial epithelial (HBE) cells. Increased NCOA4 levels and ferroptosis were confirmed in COPD. Treatment with NCOA4 siRNA and the ferroptosis inhibitor ferrostatin-1 revealed an association between ferroptosis and M2 macrophages. These findings support a role for NCOA4, which induces an increase in M2 macrophages, in the pathogenesis of COPD emphysema. Conclusion In our study, CS led to the dominance of the M2 phenotype in COPD. We identified NCOA4 as a regulator of M2 macrophages and emphysema by mediating ferroptosis, which offers a new direction for research into COPD diagnostics and treatment.

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Section: Discussionmentioning

confidence: 99%

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

Liu¹,

Zhang²,

Yang³

et al. 2022

COPD

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“…Recent findings also showed that the levels of MMP9 and MMP12 in bronchoalveolar lavage were increased in PTB patients who smoked. Between-group analysis showed that the frequency of M1 macrophages was higher in non-smoker PTB patients, while more M2 macrophages were found in smokers without PTB than in nonsmokers [125].…”

Section: Tuberculosis (Tb)mentioning

confidence: 88%

Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases

et al. 2021

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Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg168 [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg168 from OPN-R to OPN-Leu167 (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases.

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“…In our study, a substantial switch to the M2 phenotype at a later stage (72h) was observed in uninfected control macrophages compared to infected AMs, which could be due to increased expression of MMPs in control cultures. Upregulation of certain MMPs was found to be associated with macrophage polarization to both M1 and M2 phenotypes in M.tb -infected, cigarette smoke-exposed macrophages(Le et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Human alveolar macrophage response toMycobacterium tuberculosis: immune characteristics underlying large inter-individual variability

Schlesinger

Sadée

Cheeseman

et al. 2022

Preprint

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Mycobacterium tuberculosis (M.tb) establishes residence and growth in human alveolar macrophages (AMs). Large inter-individual variation in M.tb-AM interactions is a potential early indicator of TB risk and efficacy of therapies and vaccines. Herein, we systematically analyze interactions of a virulent M.tb strain with freshly isolated human AMs from healthy adult donors, measuring host RNA expression and secreted candidate proteins associated with TB pathogenesis over 72h. We observe large inter-individual differences in bacterial uptake and growth, with tenfold variation in M.tb load at 72h, reflected by large variation of gene expression programs. Systems analysis of differential and variable RNA and protein expression identifies TB-associated genes and networks (e.g., IL1B and IDO1). RNA time profiles document early stimulation of M1-type macrophage gene expression followed by emergence of an M2-type profile. The fine-scale resolution of this work enables the separation of genes and networks regulating early M.tb growth dynamics, and development of potential markers of individual susceptibility to M.tb infection and response to therapies.

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Infection of Mycobacterium tuberculosis Promotes Both M1/M2 Polarization and MMP Production in Cigarette Smoke-Exposed Macrophages

Cited by 46 publications

References 47 publications

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases

Human alveolar macrophage response toMycobacterium tuberculosis: immune characteristics underlying large inter-individual variability

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