ESAT-6 modulates Calcimycin-induced autophagy through microRNA-30a in mycobacteria infected macrophages

Behura, Assirbad; Mishra, Abtar; Chugh, Saurabh; Mawatwal, Shradha; Kumar, Ashish; Manna, Debraj; Mishra, Amit Kumar; Singh, Ramandeep; Dhiman, Rohan

doi:10.1016/j.jinf.2019.06.001

Cited by 27 publications

(14 citation statements)

References 86 publications

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“…2). It has been shown that autophagy could be tightly regulated by more than 30 highly conserved ATG genes [27], and indeed, our results supplemented the evidence for the in uence of miR-30a-5p on the Beclin-1 (ATG6) and autophagy pathways [28][29][30].…”

Section: Mir-30a-5p Overexpression Aggravates Macrophage Apoptosissupporting

confidence: 87%

MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

Geng¹,

Wang²,

Su³

et al. 2021

Preprint

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MicroRNAs are widely considered to be involved in the pathogenesis of atherosclerosis. Whereas the importance of miR-30a-5p as a tumor growth-promoting factor has been extensively studied, the relationship between this particular microRNA and atherosclerosis remains to be clarified. In this study, the role of miR-30a-5p in the formation of foam cells from THP-1-derived macrophages was investigated. It was found that miR-30a-5p could robustly regulate the pathological process of atherosclerosis by inhibiting autophagy and increasing the accumulation of lipids, the expression of inflammatory factors, and the apoptosis of macrophages. These results provide guidance for future assessments of the progression of atherosclerosis and for the development of intervention targets for the treatment of this disease.

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Section: Mir-30a-5p Overexpression Aggravates Macrophage Apoptosissupporting

confidence: 87%

MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

Geng¹,

Wang²,

Su³

et al. 2021

Preprint

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“…Based on this finding, drugs that inhibit ESX-1 may potentially attenuate M. tuberculosis infection. Studies found the early secretion antigenic target-6 (ESAT6) of ESX-1 could drive macrophages into M2 polarization [64]. Expression of ESAT6 is responsible for increased M. tuberculosis survival through modulating miR-30a production and has been identified as a phenotype favouring M. tuberculosis residence in macrophages [64].…”

Section: The Role Of Autophagy In Trained Immunity Against Mycobactermentioning

confidence: 99%

Trained immunity contributes to the prevention ofMycobacterium tuberculosisinfection, a novel role of autophagy

Zhou

Carlson

et al. 2021

Emerging Microbes & Infections

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Mycobacterium tuberculosis (M. tuberculosis) is the pathogen which causes tuberculosis (TB), a significant human public health threat. Co-infection of M. tuberculosis and the human immunodeficiency virus (HIV), emergence of drug resistant M. tuberculosis, and failure to develop highly effective TB vaccines have limited control of the TB epidemic. Trained immunity is an enhanced innate immune response which functions independently of the adaptive/acquired immune system and responds non-specifically to reinfection with invading agents. Recently, several studies have found trained immunity has the capability to control and eliminate M. tuberculosis infection. Over the past decades, however, the consensus was adaptive immunity is the only protective mechanism by which hosts inhibit M. tuberculosis growth. Furthermore, autophagy plays an essential role in the development of trained immunity. Further investigation of trained immunity, M. tuberculosis infection, and the role of autophagy in this process provide a new possibilities for vaccine development. In this review, we present the general characteristics of trained immunity and autophagy. We additionally summarize several examples where initiation of trained immunity contributes to prevention of M. tuberculosis infection and propose future directions for research in this area.

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“…Although the mechanism of early Mycobacterium –macrophage interaction influencing the subsequent macrophage response is not worked out, the pathogen internalisation is followed by alterations in a huge number of microRNAs (Table 2). In Mtb ‐infected macrophages, miR‐23a, miR‐125a, miR‐146a, miR‐579, miR‐708, miR‐27a, miR‐30a, miR‐129, miR‐1178 and miR‐1958 expressions were enhanced, whereas miR‐20b and miR‐26a expressions were downregulated 30–52 . miR23a modulates TLR2/MyD88/NF‐κB signalling to result in enhanced intracellular Mtb survival and prevention of macrophage autophagy, as miR‐23a inhibitors attenuated Mtb survival but enhanced autophagy 30 .…”

Section: Macrophage–mycobacterium Interactionmentioning

confidence: 99%

March of Mycobacterium: miRNAs intercept host cell CD40 signalling

Chauhan

Dandapat

Sarkar³

et al. 2020

Clin & Trans Imm

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The disease tuberculosis is fatal if untreated. It is caused by the acid-fast bacilli Mycobacterium tuberculosis. Mycobacterium resides and replicates within the alveolar macrophages, causing inflammation and granuloma, wherein macrophage-T cell interactions enhance the inflammation-causing pulmonary caseous lesions. The first interactions between Mycobacterium and the receptors on macrophages decide the fate of Mycobacterium because of phagolysosomal impairments and the expression of several miRNAs, which may regulate CD40 expression on macrophages. While the altered phagolysosomal functions impede antigen presentation to the T cell-expressed antigen receptor, the interactions between the macrophage-expressed CD40 and the T cell-expressed CD40-ligand (CD40L or CD154) provide signals to T cells and Mycobacterium-infected macrophages. These two functions significantly influence the resolution or persistence of Mycobacterium infection. CD40 controls T-cell polarisation and host-protective immunity by eliciting interleukin-12p40, nitric oxide, reactive oxygen species and IFN-c production. Indeed, CD40deficient mice succumb to low-dose aerosol infection with Mycobacterium because of deficient interleukin (IL)-12 production leading to impaired IFN-c-secreting T-cell response. In contrast, despite generating fewer granulomas, the CD40L-deficient mice developed anti-mycobacterial T-cell responses to the levels observed in the wild-type mice. These host-protective responses are significantly subdued by the Mycobacterium-infected macrophage produced TGF-b and IL-10, which promote promycobacterial T-cell responses. The CD40-CD40L-induced counteractive immune responses against Mycobacterium thus present a conundrum that we explain here with a reconciliatory hypothesis. Experimental validation of the hypothesis will provide a rationale for designing anti-tubercular immunotherapy.

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ESAT-6 modulates Calcimycin-induced autophagy through microRNA-30a in mycobacteria infected macrophages

Cited by 27 publications

References 86 publications

MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

Trained immunity contributes to the prevention ofMycobacterium tuberculosisinfection, a novel role of autophagy

March of Mycobacterium: miRNAs intercept host cell CD40 signalling

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