# Autophagy and Mycobacterium Tuberculosis: the role of autophagy in antimicrobial immunity and therapy

**Authors:** Hong Lei, Junya Lan, Yanan Chen, Jie Liu, Yushan Yao, Nannan Zhou, Xiudong Ding, Ying Jiang

PMC · DOI: 10.3389/fcimb.2026.1748677 · Frontiers in Cellular and Infection Microbiology · 2026-02-16

## TL;DR

This paper reviews how autophagy, a cell's self-cleaning process, can help fight tuberculosis and may lead to new treatment strategies.

## Contribution

The paper systematically reviews autophagy's role in TB immunity and highlights challenges and opportunities for autophagy-based therapies.

## Key findings

- Autophagy is crucial for eliminating Mycobacterium tuberculosis and regulating immune responses.
- M. tb can evade autophagy, complicating therapeutic strategies.
- Autophagy modulators show promise as adjunct therapies for TB.

## Abstract

Tuberculosis (TB) remains one of the most severe infectious diseases worldwide, posing a persistent and increasingly serious threat to global public health. Cellular autophagy, a highly conserved innate immune mechanism, plays a crucial role in the elimination of intracellular pathogens, regulation of immune responses, and maintenance of cellular homeostasis, making it a key focus in TB research. This review systematically summarizes the types and regulatory mechanisms of autophagy, as well as its interactions with Mycobacterium tuberculosis (M. tb), and explores the potential applications of autophagy-based host-directed therapeutic strategies. It also addresses the major challenges in current research, including the complex mechanisms by which M. tb evades autophagy, the selectivity and safety concerns of autophagy modulators, and the technical barriers to clinical translation. Growing evidence suggests that autophagy has emerged as a promising therapeutic target for TB, and autophagy modulators may serve as effective adjunctive therapies. Future research should further elucidate the interactions between autophagy and immunometabolic pathways, optimize the targeted delivery of autophagy activators, and verify their efficacy and safety through systematic clinical studies, thereby providing new theoretical foundations and therapeutic strategies for TB prevention and treatment.

## Linked entities

- **Diseases:** tuberculosis (MONDO:0018076)
- **Species:** Mycobacterium tuberculosis (taxon 1773)

## Full-text entities

- **Genes:** IL-6 [NCBI Gene 493687], CD4 [NCBI Gene 493775], ATG8 (ubiquitin-like protein ATG8) [NCBI Gene 852200] {aka APG8, AUT7, CVT5}, ATG3 (Atg3p) [NCBI Gene 855741] {aka APG3, AUT1}, ATG12 (Atg12p) [NCBI Gene 852518] {aka APG12}, ATG10 (E2-like conjugating enzyme) [NCBI Gene 850684] {aka APG10}, ATG16 (Atg16p) [NCBI Gene 855194] {aka APG15, APG16, CVT11, SAP18}, ATG14 (Atg14p) [NCBI Gene 852425] {aka APG14, CVT12}, VPS30 (beclin 1) [NCBI Gene 855983] {aka APG6, ATG6, VPT30}, VPS15 (ubiquitin-binding serine/threonine protein kinase VPS15) [NCBI Gene 852394] {aka GRD8, VAC4, VPL19, VPS40, VPT15}, TNF-alpha [NCBI Gene 493755], ATG4 (cysteine protease ATG4) [NCBI Gene 855498] {aka APG4, AUT2}, VPS34 (phosphatidylinositol 3-kinase VPS34) [NCBI Gene 850941] {aka END12, PEP15, STT8, VPL7, VPS7, VPT29}, ATG7 (Atg7p) [NCBI Gene 856576] {aka APG11, APG7, CVT2}, ATG5 (Atg5p) [NCBI Gene 855954] {aka APG5}, UBI4 (ubiquitin) [NCBI Gene 850620] {aka SCD2, UB14}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, ATG13 (serine/threonine protein kinase regulatory subunit ATG13) [NCBI Gene 856315] {aka APG13}
- **Diseases:** pulmonary inflammation (MESH:D011014), Granuloma (MESH:D006099), M. tb infection (MESH:D014376), tumorigenesis (MESH:D063646), PIM (MESH:D009800), musculoskeletal diseases (MESH:D009140), bacterial infection (MESH:D001424), hypoxia (MESH:D000860), infectious disease (MESH:D003141), necrosis (MESH:D009336), metabolic disorders (MESH:D008659), reproductive dysfunction (MESH:D060737), ocular disorders (MESH:D005128), deaths (MESH:D003643), nutrient deficiency (MESH:D007153), inflammation (MESH:D007249), neurodegenerative diseases (MESH:D019636), HL (MESH:C538324), lung tissue damage (MESH:D055370), cytotoxicity (MESH:D064420), nutrient insufficiency (MESH:D000309), cancer (MESH:D009369), infection (MESH:D007239)
- **Chemicals:** phenylbutyrate (MESH:D010654), glycogen (MESH:D006003), PI3P (MESH:C055525), Gln (MESH:D005973), steroid (MESH:D013256), ATP (MESH:D000255), AMP (MESH:D000249), calcium (MESH:D002118), ROS (MESH:D017382), PIM (MESH:C034154), cholesterol (MESH:D002784), glucose (MESH:D005947), Glutamate (MESH:D018698), clofazimine (MESH:D002991), simvastatin (MESH:D019821), 1,25-dihydroxyvitamin D3 (MESH:D002117), isoniazid (MESH:D007538), oxygen (MESH:D010100), everolimus (MESH:D000068338), phosphorus (MESH:D010758), PI (MESH:D010716), pyrazinamide (MESH:D011718), Vitamin D (MESH:D014807), PE (MESH:C483858), rifampicin (MESH:D012293), Arginine (MESH:D001120), fatty acid (MESH:D005227), Rapamycin (MESH:D020123), ADP (MESH:D000244), Phe (MESH:D010649), LAM (MESH:C050016), Vitamin D3 (MESH:D002762), amino acids (MESH:D000596), nitrogen (MESH:D009584), RNS (MESH:D026361)
- **Species:** Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mycobacterium tuberculosis (species) [taxon 1773], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12950778/full.md

## References

110 references — full list in the complete paper: https://tomesphere.com/paper/PMC12950778/full.md

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Source: https://tomesphere.com/paper/PMC12950778