The Multifaceted Roles of Autophagy in Infectious, Obstructive, and Malignant Airway Diseases

Carinci, Marianna; Palumbo, Laura; Pellielo, Giulia; Agyapong, Esther Densu; Morciano, Giampaolo; Patergnani, Simone; Giorgi, Carlotta; Pinton, Paolo; Rimessi, Alessandro

doi:10.3390/biomedicines10081944

Cited by 5 publications

(6 citation statements)

References 244 publications

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“…Apoptotic cell death, in particular, is a defense technique cells use to resist intracellular infections [ 8 ]. In contrast, necrotic death is unregulated, allowing Mtb to disseminate to proximal cells upon lytic death [ 9 ]. Autophagy is also crucial in the regulation of Mtb.…”

Section: Discussionmentioning

confidence: 99%

“…Current transcriptome investigations have identified several genes and gene expression patterns associated with tuberculosis pathogenesis. The death of host cells is critical for Mtb infection control, as it prevents mycobacterial growth and dissemination [7][8][9]. Apoptotic cell death, in particular, is a defense technique cells use to resist intracellular infections [8].…”

Section: Discussionmentioning

confidence: 99%

“…Host cell apoptosis is essential for controlling Mtb infection [7,8]. Numerous genetic fingerprints that indicate the pathogenic process and serve as unique biomarkers for separating ATB from LTBI have been discovered [7][8][9]. In the body's regular physiological functioning, autophagy plays a role in maintaining cellular homeostasis and survival.…”

Section: Introductionmentioning

confidence: 99%

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Autophagy-related molecular clusters identified as indicators for distinguishing active and latent TB infection in pediatric patients

Yu,

Hua,

Chen

2024

BMC Pediatr

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Background Autophagy is crucial for controlling the manifestation of tuberculosis. This study intends to discover autophagy-related molecular clusters as biomarkers for discriminating between latent tuberculosis (LTBI) and active tuberculosis (ATB) in children through gene expression profile analysis. Methods The expression of autophagy modulators was examined in pediatric patients with LTBI and ATB utilizing public datasets from the Gene Expression Omnibus (GEO) collection (GSE39939 and GSE39940). Results In a training dataset (GSE39939), patients with LTBI and ATB exhibited the expression of autophagy-related genes connected with their active immune responses. Two molecular clusters associated with autophagy were identified. Compared to Cluster 1, Cluster 2 was distinguished through decreased adaptive cellular immune response and enhanced inflammatory activation, according to single-sample gene set enrichment analysis (ssGSEA). Per the study of gene set variation, Cluster 2’s differentially expressed genes (DEGs) played a role in synthesizing transfer RNA, DNA repair and recombination, and primary immunodeficiency. The peak variation efficiency, root mean square error, and area under the curve (AUC) (AUC = 0.950) were all lowered in random forest models. Finally, a seven-gene-dependent random forest profile was created utilizing the CD247, MAN1C1, FAM84B, HSZFP36, SLC16A10, DTX3, and SIRT4 genes, which performed well against the validation dataset GSE139940 (AUC = 0.888). The nomogram calibration and decision curves performed well in identifying ATB from LTBI. Conclusions In summary, according to the present investigation, autophagy and the immunopathology of TB might be correlated. Furthermore, this investigation established a compelling prediction expression profile for measuring autophagy subtype development risks, which might be employed as possible biomarkers in children to differentiate ATB from LTBI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Autophagy-related molecular clusters identified as indicators for distinguishing active and latent TB infection in pediatric patients

Yu,

Hua,

Chen

2024

BMC Pediatr

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“…Autophagy is widely recognized as a crucial defense mechanism that represents a possible therapeutic target to enhance innate immunity against infectious diseases [ 38 , 39 ]. While many studies have provided evidence for a protective role of autophagy in infections with Mtb or other mycobacteria, it is still not well understood how these notorious pathogens interact with the autophagy machinery [ 7 , 21 , 40 , 41 , 42 , 43 , 44 ]. First, the differential roles of autophagy versus autophagy-related pathways, such as LAP, in mycobacterial host defense remain to be dissected.…”

Section: Discussionmentioning

confidence: 99%

Using Zebrafish to Dissect the Interaction of Mycobacteria with the Autophagic Machinery in Macrophages

Muñoz-Sánchez

Varela

Vaart

et al. 2023

Biology

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Existing drug treatment against tuberculosis is no match against the increasing number of multi-drug resistant strains of its causative agent, Mycobacterium tuberculosis (Mtb). A better understanding of how mycobacteria subvert the host immune defenses is crucial for developing novel therapeutic strategies. A potential approach is enhancing the activity of the autophagy machinery, which can direct bacteria to autophagolysosomal degradation. However, the interplay specifics between mycobacteria and the autophagy machinery must be better understood. Here, we analyzed live imaging data from the zebrafish model of tuberculosis to characterize mycobacteria-autophagy interactions during the early stages of infection in vivo. For high-resolution imaging, we microinjected fluorescent Mycobacterium marinum (Mm) into the tail fin tissue of zebrafish larvae carrying the GFP-LC3 autophagy reporter. We detected phagocytosed Mm clusters and LC3-positive Mm-containing vesicles within the first hour of infection. LC3 associations with these vesicles were transient and heterogeneous, ranging from simple vesicles to complex compound structures, dynamically changing shape by fusions between Mm-containing and empty vesicles. LC3-Mm-vesicles could adopt elongated shapes during cell migration or alternate between spacious and compact morphologies. LC3-Mm-vesicles were also observed in cells reverse migrating from the infection site, indicating that the autophagy machinery fails to control infection before tissue dissemination.

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“…Acute exposure to cigarette smoke may activate autophagy, resulting in ciliary dysfunction and death of airway epithelial cells [ 111 ]. It is challenging to target autophagy therapeutically since the level of autophagy might vary from cell type to cell type and from one environment to another inside a cell [ 112 ]. However, these medications are not specific, and researchers are currently working on developing drugs that are more selective.…”

Section: Targeting Autophagy Modulation To Eliminate Environmental Su...mentioning

confidence: 99%

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

Rahman

Parvez

et al. 2023

Toxics

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Autophagy is an evolutionarily conserved cellular system crucial for cellular homeostasis that protects cells from a broad range of internal and extracellular stresses. Autophagy decreases metabolic load and toxicity by removing damaged cellular components. Environmental contaminants, particularly industrial substances, can influence autophagic flux by enhancing it as a protective response, preventing it, or converting its protective function into a pro-cell death mechanism. Environmental toxic materials are also notorious for their tendency to bioaccumulate and induce pathophysiological vulnerability. Many environmental pollutants have been found to influence stress which increases autophagy. Increasing autophagy was recently shown to improve stress resistance and reduce genetic damage. Moreover, suppressing autophagy or depleting its resources either increases or decreases toxicity, depending on the circumstances. The essential process of selective autophagy is utilized by mammalian cells in order to eliminate particulate matter, nanoparticles, toxic metals, and smoke exposure without inflicting damage on cytosolic components. Moreover, cigarette smoke and aging are the chief causes of chronic obstructive pulmonary disease (COPD)-emphysema; however, the disease’s molecular mechanism is poorly known. Therefore, understanding the impacts of environmental exposure via autophagy offers new approaches for risk assessment, protection, and preventative actions which will counter the harmful effects of environmental contaminants on human and animal health.

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The Multifaceted Roles of Autophagy in Infectious, Obstructive, and Malignant Airway Diseases

Cited by 5 publications

References 244 publications

Autophagy-related molecular clusters identified as indicators for distinguishing active and latent TB infection in pediatric patients

Autophagy-related molecular clusters identified as indicators for distinguishing active and latent TB infection in pediatric patients

Using Zebrafish to Dissect the Interaction of Mycobacteria with the Autophagic Machinery in Macrophages

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

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