Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages

Cheng, Yong; Kiene, Nicholas J.; Tatarian, Alexandra; Eix, Emily F; Schorey, Jeffrey S.

doi:10.1371/journal.ppat.1008569

Cited by 11 publications

(8 citation statements)

References 35 publications

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“…Cheng et al indicated that the host cytosolic RNA sensing pathway stimulates ICAM-1 expression through the inhibition of CRL4 COP1/DET1 , an E3 ubiquitin ligase, and promotes T Lymphocyte-mediated mycobacterial killing in macrophages. 30 Jia et al found that Gal9 can be recruited by impaired lysosomes to regulate ubiquitination and contribute to autophagic control during Mtb infection. 31 Additionally, Chai et al demonstrated that Mtb surface protein Rv1468c could recruit ubiquitin to trigger host xenophagy.…”

Section: Discussionmentioning

confidence: 99%

<p>Profiling the mRNA and miRNA in Peripheral Blood Mononuclear Cells in Subjects with Active Tuberculosis</p>

Cao¹,

Ju²,

Ji³

et al. 2020

IDR

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To identify candidate hub genes and miRNAs associated with active tuberculosis (ATB) and reveal the potential molecular mechanisms of disease progression. Patients and Methods: The expression of mRNA and miRNA was evaluated in peripheral blood mononuclear cells (PBMC) from 4 ATB patients and 4 healthy donors (HD) using high throughput sequencing (HTS) and bioinformatics analysis. Moreover, differentially expressed miRNAs were validated with 35 ATB patients and 35 HDs using reverse transcription quantitative real-time PCR (RT-qPCR). Results: A total of 2658 significantly differentially expressed genes (DEG) including 1415 up-regulated genes and 1243 down-regulated genes were identified in the ATB group compared with HDs, and the DEGs enriched in immune-related pathways, especially in TNF signaling pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathways and tuberculosis. Additionally, 10 hub genes were acquired according to protein-protein interaction (PPI) analysis of DEGs. Moreover, 26 differentially expressed miRNAs were found in ATB group compared with HDs. Furthermore, RT-qPCR results showed that hsa-miR-23a-5p (P=0.0106), hsa-miR-183-5p (P=0.0027), hsa-miR-193a-5p (P=0.0021) and hsa-miR-941(P=0.0001) were significantly increased in the ATB patients compared with HD group, and the hsa-miR-16-1-3p was significantly decreased (P=0.0032). Conclusion: Our research provided a characteristic profile of mRNAs and miRNAs expressed in ATB subjects, and 10 hub genes related with ATB were found, which will contribute to explore the role of miRNAs and hub genes in the pathogenesis of ATB, and improve the ability of differential diagnosis and treatment for the disease.

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Section: Discussionmentioning

confidence: 99%

<p>Profiling the mRNA and miRNA in Peripheral Blood Mononuclear Cells in Subjects with Active Tuberculosis</p>

Cao¹,

Ju²,

Ji³

et al. 2020

IDR

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“…No. M198; HiMedia Laboratories) containing 10% OADC (oleic acid/albumin/dextrose/catalase, 0.05% Tween 80) as we did previously [12] until midexponential phase. Prior to use, bacterial culture was passed through a syringe fitted with a 27‐gauge needle at least 10 times.…”

Section: Methodsmentioning

confidence: 99%

“…No. M198; HiMedia Laboratories) containing 10% OADC (oleic acid/albumin/dextrose/catalase, 0.05% Tween 80) as we did previously [12] until midexponential phase.…”

Section: Bacterial Culturementioning

confidence: 99%

Mycobacterium abscessus extracellular vesicles increase mycobacterial resistance to clarithromycin in vitro

Vermeire,

Tan,

Liang

et al. 2024

Proteomics

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Nontuberculous Mycobacteria (NTM) are a group of emerging bacterial pathogens that have been identified in cystic fibrosis (CF) patients with microbial lung infections. The treatment of NTM infection in CF patients is challenging due to the natural resistance of NTM species to many antibiotics. Mycobacterium abscessus is one of the most common NTM species found in the airways of CF patients. In this study, we characterized the extracellular vesicles (EVs) released by drug‐sensitive M. abscessus untreated or treated with clarithromycin (CLR), one of the frontline anti‐NTM drugs. Our data show that exposure to CLR increases mycobacterial protein trafficking into EVs as well as the secretion of EVs in culture. Additionally, EVs released by CLR‐treated M. abscessus increase M. abscessus resistance to CLR when compared to EVs from untreated M. abscessus. Proteomic analysis further indicates that EVs released by CLR‐treated M. abscessus carry an increased level of 50S ribosomal subunits, the target of CLR. Taken together, our results suggest that EVs play an important role in M. abscessus resistance to CLR treatment.

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“…Host cytosolic RNA-sensing pathways play a critical role in sensing the DNA and RNA of intracellular pathogens, including Listeria monocytogenes and M. tuberculosis (Mtb) ( 34 , 35 ). The host cytosolic RNA-sensing pathway facilitates T cell-mediated bacterial killing in M. avium -infected macrophages ( 36 ). In macrophages, RNA released from MAC-containing phagosomes and retinoic acid inducible gene-I (RIG-I) recognizes the released RNA ( Figure 2 ).…”

Section: Understanding the Innate Immune Response To Mac Infectionmentioning

confidence: 99%

“…The nuclear translocation of ETV5 induces the expression of intracellular adhesion molecule-1 (ICAM-1) which, along with type I interferon expression, induces T lymphocyte-mediated mycobacterial killing in macrophages. In contrast to Mtb infection, activation of the host RNA-sensing pathway provides host protection against M. avium infection ( 36 ).…”

Section: Understanding the Innate Immune Response To Mac Infectionmentioning

confidence: 99%

Modulating macrophage function to reinforce host innate resistance against Mycobacterium avium complex infection

et al. 2022

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Mycobacterium avium complex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental media such as soil as well as in domestic and natural waters. MAC is a primary causative agent of NTM-lung disease that threaten immunocompromised or structural lung disease patients. The incidence and the prevalence of M. tuberculosis infection have been reduced, while MAC infections and mortality rates have increased, making it a cause of global health concern. The emergence of drug resistance and the side effects of long-term drug use have led to a poor outcome of treatment regimens against MAC infections. Therefore, the development of host-directed therapy (HDT) has recently gained interest, aiming to accelerate mycobacterial clearance and reversing lung damage by employing the immune system using a novel adjuvant strategy to improve the clinical outcome of MAC infection. Therefore, in this review, we discuss the innate immune responses that contribute to MAC infection focusing on macrophages, chief innate immune cells, and host susceptibility factors in patients. We also discuss potential HDTs that can act on the signaling pathway of macrophages, thereby contributing to antimycobacterial activity as a part of the innate immune response during MAC infection. Furthermore, this review provides new insights into MAC infection control that modulates and enhances macrophage function, promoting host antimicrobial activity in response to potential HDTs and thus presenting a deeper understanding of the interactions between macrophages and MACs during infection.

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Host cytosolic RNA sensing pathway promotes T Lymphocyte-mediated mycobacterial killing in macrophages

Cited by 11 publications

References 35 publications

<p>Profiling the mRNA and miRNA in Peripheral Blood Mononuclear Cells in Subjects with Active Tuberculosis</p>

<p>Profiling the mRNA and miRNA in Peripheral Blood Mononuclear Cells in Subjects with Active Tuberculosis</p>

Mycobacterium abscessus extracellular vesicles increase mycobacterial resistance to clarithromycin in vitro

Modulating macrophage function to reinforce host innate resistance against Mycobacterium avium complex infection

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