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Recognition of Mycobacterium tuberculosis by macrophage Toll-like receptor and its role in autophagy

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Abstract

Background

The pathogen responsible for tuberculosis is called Mycobacterium tuberculosis. Its interaction with macrophages has a significant impact on the onset and progression of the disease.

Methods

The respiratory pathway allows Mycobacterium tuberculosis to enter the body's lungs where it battles immune cells before being infected latently or actively. In the progress of tuberculosis, Mycobacterium tuberculosis activates the body's immune system and creates inflammatory factors, which cause tissue inflammation to infiltrate and the creation of granulomas, which seriously harms the body. Toll-like receptors of macrophage can mediate host recognition of Mycobacterium tuberculosis, initiate immune responses, and participate in macrophage autophagy. New host-directed therapeutic approaches targeting autophagy for drug-resistant Mycobacterium tuberculosis have emerged, providing new ideas for the effective treatment of tuberculosis.

Conclusions

In-depth understanding of the mechanisms by which macrophage autophagy interacts with intracellular Mycobacterium tuberculosis, as well as the study of potent and specific autophagy-regulating molecules, will lead to much-needed advances in drug discovery and vaccine design, which will improve the prevention and treatment of human tuberculosis.

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Fig. 1

Note: Toll-like receptors, which identify molecules with conserved structures derived from MTB, are a significant class of protein molecules involved in non-specific immunity. TLR1, TLR2, TLR4, and LTR6 are surface receptors on macrophages. TLR2 can work in concert with TLR1 and TLR6 to recognize molecules of various MTB PMAPs combinatorially. Also, TLR4 is capable of identifying multiple MTB ligands. TLR3, TLR7, TLR8, and TLR9 located in the endosomal/lysosomal compartment and are involved in the recognition of nucleic acid components of MTB

Fig. 2

Note: TLR2 forms a heterodimer with TLR1/TLR6 upon identification of the macrophage surface Toll-like receptor by MTB ligands, hence initiating the MyD88-dependent pathway. TLR7/8 and TLR9 also cause the MyD88-dependent pathway to become active. When TLR4 recognizes the appropriate ligands, it activates both the MyD88-dependent and MyD88-independent pathways (TRIF pathway). Only the MyD88 independent pathway is triggered by TLR3. The TIR structural domain of TLRs changes shape when the extracellular region identifies the matching PAMPs, and the C-terminus keeps attracting MyD88 or other junctional proteins. After IRAK is recruited by MyD88 through KD, downstream signaling via TRAF6, TAK1, TAB1, and 2 is started, activating NF-κB or AP-1 and causing the production of inflammatory cytokines. MyD88 non-dependent pathway activation via TRIF and TRAF3 leads to IKKε/TBK1 recruitment, IRF3 phosphorylation and IFN-β expression

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Data availability

The data that support the findings of this review are openly available in public resources.

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Acknowledgements

We acknowledge the funding support from the National Nature Science Foundation of China (NSFC) (No. 81860291).

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  1. Department of Immunology, Zunyi Medical University, Zunyi, 563000, China

    Linna Wei, Liping Liu, Zudi Meng, Kai Qi, Xuehan Gao & Junmin Luo

  2. Department of Oncology, Lishui People’s Hospital, Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, Zhejiang, China

    Jihong Feng

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Junmin Luo, Jihong Feng contributed to the conception of the review; Linna Wei wrote the manuscript; Liping Liu performed manuscript preparation contributed collection; Zudi Meng, Kai Qi, Xuehan Gao helped perform constructive discussions.

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Wei, L., Liu, L., Meng, Z. et al. Recognition of Mycobacterium tuberculosis by macrophage Toll-like receptor and its role in autophagy. Inflamm. Res. 73, 753–770 (2024). https://doi.org/10.1007/s00011-024-01864-x

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