Evaluation of the expression of cytokines and chemokines in macrophages in response to rifampin-monoresistant Mycobacterium tuberculosis and H37Rv strain

Ravan, Parvaneh; Sattari, Taher Nejad; Siadat, Seyed Davar; Vaziri, Farzam

doi:10.1016/j.cyto.2018.12.004

Cited by 3 publications

(2 citation statements)

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“…Proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were reported to play crucial roles in promoting the progression of TB ( Nair et al, 2009 ; Gong et al, 2019 ; Ravan et al, 2019 ). To determine whether miR-27a-3p and miR-30b-5p are related to TB progression by regulating the secretion of proinflammatory cytokines, we transfected miR-27a-3p and miR-30b-5p mimics and inhibitors into cells and measured proinflammatory cytokine secretion.…”

Section: Resultsmentioning

confidence: 99%

MiR-27a-3p and miR-30b-5p inhibited-vitamin D receptor involved in the progression of tuberculosis

Xiao

Yang²,

Zhou³

et al. 2022

Front. Microbiol.

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BackgroundMicroRNAs (miRNAs) play a vital role in tuberculosis (TB). Vitamin D receptor (VDR), an miRNA target gene, and its ligand, vitamin D3 (VitD3), have been reported to exert protective effects against TB. However, whether miRNAs can affect the progression of TB by targeting VDR has not been reported.Materials and methodsResearch subjects were selected according to defined inclusion criteria. A clinical database of 360 samples was established, including the subjects’ demographic information, miRNA expression profiles and cellular experimental results. Two candidate miRNAs, miR-27a-3p, and miR-30b-5p, were identified by a high-throughput sequencing screen and validated by qRT–PCR assays. Univariate and multivariate statistical analyses were performed. VDR and NF-kB p65 protein levels were detected by Western blot assays. Proinflammatory cytokine expression levels were detected by enzyme-linked immunosorbent assay (ELISA). Luciferase assays and fluorescence-activated cell sorting (FACS) were further applied to elucidate the detailed mechanisms.ResultsDifferential miRNA expression profiles were obtained, and miR-27a-3p and miR-30b-5p were highly expressed in patients with TB. These results showed that the two miRNAs were able to induce M1 macrophage differentiation and inhibit M2 macrophage differentiation. Further experiments showed that the two miRNAs decreased the VDR protein level and increased proinflammatory cytokine secretion by macrophages. Mechanistically, the miRNAs targeted the 3′ untranslated region (3′UTR) of the VDR mRNA and thereby downregulated VDR protein levels by post-transcriptional regulation. Then, due to the reduction in VDR protein levels, the NF-kB inflammatory cytokine signaling pathway was activated, thus promoting the progression of TB.ConclusionOur study not only identified differentially expressed miRNAs between the TB and control groups but also revealed that miR-27a-3p and miR-30b-5p regulate proinflammatory cytokine secretion and macrophage differentiation through VDR in macrophages. Thus, these two miRNAs influence the progression of TB.

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Section: Resultsmentioning

confidence: 99%

MiR-27a-3p and miR-30b-5p inhibited-vitamin D receptor involved in the progression of tuberculosis

Xiao

Yang²,

Zhou³

et al. 2022

Front. Microbiol.

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“…M. tb infects macrophages and persists in human macrophages for a prolonged period of time by escaping the host immune defense system (Pieters, 2008). M. tb has evolved multiple mechanisms to interfere with a wide range of host cellular processes, such as the modulation of macrophage survival (Queval et al, 2017), the production of cytokines (Ravan et al, 2019), reactive oxygen and nitrogen species (Tiwari et al, 2018;Mehta and Singh, 2019), the blockage of phagosome maturation (Zulauf et al, 2018), microtubule-associated light chain 3-associated phagocytosis and autophagy (Simmons et al, 2018). Tremendous efforts have been made to understand how M. tb survives in macrophages.…”

Section: Introductionmentioning

confidence: 99%

PE_PGRS31-S100A9 Interaction Promotes Mycobacterial Survival in Macrophages Through the Regulation of NF-κB-TNF-α Signaling and Arachidonic Acid Metabolism

et al. 2020

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Mycobacterium tuberculosis (M. tb) evades the surveillance of immune responses for survival in macrophages. However, the precise mechanism and toxins/proteins encoded by M. tb involved in the bacterial escape remain elusive. The function of Rv1768 protein (also referred to as PE_PGRS31, belonging to the PE_PGRS family) encoded by the region of deletion 14 (RD-14) in the virulent M. tb H37Rv strain has not, to the best of our knowledge, been reported previously. Here, we found that Rv1768 remarkably promotes bacterial survival in macrophages. Compared to wild type (WT) H37Rv, the Rv1768 deficient strain (H37Rv 1768) showed significantly decreased colony-forming units in the lungs, spleen, and liver of the murine M. tb infection model. The bacterial burdens of WT H37Rv in WT macrophages and C57BL/6 mice were significantly higher than those in S100A9 deficiency cells and mice, but there were no significant differences for H37Rv Rv1768. Rv1768 binds S100A9 with the proline-glutamic acid domain (PE domain) and blocks the interaction between S100A9 and Toll-like receptor 4 (TLR4), and suppresses TLR4-myeloid differentiation factor 88-nuclear factor-kappa B (NF-κB)-tumor necrosis factor α (TNF-α) signaling in macrophages. Interestingly, Rv1768 binding to S100A9 also disturbs the metabolism of arachidonic acid by activating 5-lipoxygenase, increasing lipotoxin A4, and down-regulating cyclooxygenase-2 and prostaglandin E2 expression, thus, promoting mycobacterial survival. Our results revealed that M. tb Rv1768 promotes mycobacterial survival in macrophages by regulating NF-κB-TNF-α signaling and arachidonic acid metabolism via S100A9. Disturbing the interaction between Rv1768 and S100A9 may be a potential therapeutic target for tuberculosis.

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Evolution of Drug-Resistant Mycobacterium tuberculosis Strains and Their Adaptation to the Human Lung Environment

2021

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In the last two decades, multi (MDR), extensively (XDR), extremely (XXDR) and total (TDR) drug-resistant Mycobacterium tuberculosis (M.tb) strains have emerged as a threat to public health worldwide, stressing the need to develop new tuberculosis (TB) prevention and treatment strategies. It is estimated that in the next 35 years, drug-resistant TB will kill around 75 million people and cost the global economy $16.7 trillion. Indeed, the COVID-19 pandemic alone may contribute with the development of 6.3 million new TB cases due to lack of resources and enforced confinement in TB endemic areas. Evolution of drug-resistant M.tb depends on numerous factors, such as bacterial fitness, strain’s genetic background and its capacity to adapt to the surrounding environment, as well as host-specific and environmental factors. Whole-genome transcriptomics and genome-wide association studies in recent years have shed some insights into the complexity of M.tb drug resistance and have provided a better understanding of its underlying molecular mechanisms. In this review, we will discuss M.tb phenotypic and genotypic changes driving resistance, including changes in cell envelope components, as well as recently described intrinsic and extrinsic factors promoting resistance emergence and transmission. We will further explore how drug-resistant M.tb adapts differently than drug-susceptible strains to the lung environment at the cellular level, modulating M.tb–host interactions and disease outcome, and novel next generation sequencing (NGS) strategies to study drug-resistant TB.

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Evaluation of the expression of cytokines and chemokines in macrophages in response to rifampin-monoresistant Mycobacterium tuberculosis and H37Rv strain

Cited by 3 publications

References 50 publications

MiR-27a-3p and miR-30b-5p inhibited-vitamin D receptor involved in the progression of tuberculosis

MiR-27a-3p and miR-30b-5p inhibited-vitamin D receptor involved in the progression of tuberculosis

PE_PGRS31-S100A9 Interaction Promotes Mycobacterial Survival in Macrophages Through the Regulation of NF-κB-TNF-α Signaling and Arachidonic Acid Metabolism

Evolution of Drug-Resistant Mycobacterium tuberculosis Strains and Their Adaptation to the Human Lung Environment

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