Advances in the Study of the Molecular Mechanisms of Macrophage Polarization in Mycobacterium Tuberculosis Infection

DOI: https://doi.org/10.62517/jmhs.202605205

Author(s)

Qing Xue

Affiliation(s)

Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

Abstract

Mycobacterium tuberculosis (Mtb) infection-related tuberculosis is still a significant worldwide public health concern. The host immune response is insufficient to completely eliminate the pathogen, resulting in the formation of complex, dynamically evolving tuberculous granulomas, which are its main pathological feature. Granulomas serve as both a host defense structure limiting Mtb spread and a microenvironment for bacterial immune evasion and latent survival. In this process, macrophages, as the primary host cells for Mtb, play a crucial role, with the dynamic balance of their M1/M2 polarization determining the formation, maintenance, and outcome of granulomas. This article systematically reviews the multiple molecular mechanisms regulating macrophage polarization in tuberculous granulomas, focusing on the roles of host transcription factors, non-coding RNAs, metabolites, and Mtb effector proteins, aiming to provide new insights for host-guided therapy of tuberculosis.

Keywords

Mycobacterium Tuberculosis; Granuloma; Macrophage Polarization; M1/M2

References

[1]Martinez F O, Sica A, Mantovani A, et a1. Macrophage activation and po1arization. Front Biosci, 2008, 13: 453-61. [2]Atrl C, Guerfali F Z, Laouini D. Ro1e of Human Macrophage Po1arization in lnflammation during lnfectious Diseases. lnt J Mol Sci, 2018, 19(6). [3]Huang Z, Luo Q, Guo Y, et al. Mycobacterium tubercu1osis-lnduced Po1arization of Human Macrophage Orchestrates the Formation and Deve1opment of Tubercu1ous Granu1omas In Vitro. PLoS One, 2015, 10(6): e0129744. [4]Yunna C, Mengru H, Lei W, et a1. Macrophage M1/M2 po1arization. Eur J Pharmaco1, 2020, 877: 173090. [5]Zafar A, Ng H P, Kim G D, et a1. BHLHE40 promotes macrophage pro-inflammatory gene expression and functions. Faseb j, 2021, 35(10): e21940. [6]Hendrix S V, Mreyoud Y, McNeh1an M E, et a1. BHLHE40 Regu1ates Mye1oid Cell Po1arization through lL-10-Dependent and -lndependent Mechanisms. J Immunol, 2024, 212(11): 1766-81. [7]Cramer T, Yamanishi Y, Clausen B E, et a1. HIF-1alpha is essential for mye1oid cell-mediated inf1ammation. Cell, 2003, 112(5): 645-57. [8]Nakamlzo S, Kabashlma K. Metabolic reprogramming and macrophage po1arization in granu1oma formation. lnt lmmuno1, 2024, 36(7): 329-38. [9]Atianand M K, Caffrey D R, Fitzgera1d K A. lmmunobiology of Long Noncoding RNAs. Annu Rev lmmunol, 2017, 35: 177-98. [10]Li D, Gao C, Zhao L, et a1. lnflammatory response is modu1ated by 1incRNACox2 via the NF‑κb pathway in macrophages lnfected by Mycobacterium tubercu1osis. Mol Med Rep, 2020, 21(6): 2513-21. [11]Carey A J, Tan C K, U1ett G C. lnfection-induced lL-10 and JAK-STAT: A review of the mo1ecular circuitry controlling immune hyperactivity in response to pathogenic microbes. Jakstat, 2012, 1(3): 159-67. [12]Kulcheski F R, Christoff A P, Margls R. Circu1ar RNAs are miRNA sponges and can be used as a new c1ass of biomarker. J Biotechnol, 2016, 238: 42-5l. [13]Peng Y, Wu X J, Ji X J, et al. Circu1ar RNA circTRAPPC6B Enhances lL-6 and lL-1β Expression and Repo1arizes Mycobacteria lnduced Macrophages from M2- to M1-Like Phenotype by Targeting miR-892c-3p. J lnterferon Cytokine Res, 2023, 43(6): 269-79. [14]Cho H Y, Ahn S, Cho Y S, et a1. CYP2C19 Contributes to THP-1-Ce11-Derived M2 Macrophage Polarization by Producing 11,12- and 14,15-Epoxyeicosatrienoic Acid, Agonists of the PPARγ Receptor. Pharmaceuticals (Basel), 2023, 16(4). [15]Yang J, Yang L, Tian L, et a1. Sphingosine l-Phosphate (SlP)/SlP Receptor2/3 Axls Promotes lnflammatory M1 Polarization of Bone Marrow-Derived Monocyte/Macrophage via G(α)i/O/PI3K/JNK Pathway. Ce11 Physiol Biochem, 2018, 49(5): 1677-93. [16]Arish M, Naz F. Sphingosine-1-phosphate receptors 2 and 3 reprogram resting human macrophages into Ml phenotype fo11owing mycobacteria infection. Curr Res Immuno1, 2022, 3: 110-7. [17]Sun F, Li J, Cao L, et a1. Mycobacterium tubercu1osis viru1ence protein ESAT-6 inf1uences M1/M2 po1arization and macrophage apoptosis to regulate tubercu1osis progression. Genes Genomics, 2024, 46(1): 37-47. [18]Zhou L, Luo L, Luo L, et a1. Ag85B-lnduced M1 Macrophage Po1arization via the TLR4/TRAF6/NF-κB Axls 1eading to Bronchial Epithelial Ce1l Damage and TH17/Treg lmbalance. Curr Mo1 Med, 2025. [19]Zheng Q, Li Z, Zhou Y, et al. Heparin-Binding Hemagg1utinin of Mycobacterium tubercu1osis lnhibits Autophagy via To11-like Receptor 4 and Drives M2 Po1arization in Macrophages. J 1nfect Dis, 2024, 230(2): 323-35.