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Rv2741 Promotes Mycobacterium Survival by Modulating Macrophage Function via the IL-1α-MAPK Axis

Xintong He1, Yonglin He1, Xichuan Deng2

  • 1Department of Pathogenic Biology, School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.

ACS Infectious Diseases
|February 26, 2025
PubMed

Insights

Tuberculosis (TB) involves PE_PGRS proteins like Rv2741, which aids Mycobacterium tuberculosis survival. This study shows Rv2741 inhibits host immune responses, including IL-1α secretion and MAPK signaling, promoting bacterial virulence.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Tuberculosis (TB) remains a global health challenge caused by Mycobacterium tuberculosis (M. tuberculosis).
  • PE_PGRS proteins are crucial for M. tuberculosis pathogenicity and immune evasion, but their functions are largely unknown.
  • The Rv2741 (PE_PGRS47) gene, unique to pathogenic mycobacteria, is investigated for its role in host-pathogen interactions.

Purpose of the Study:

  • To elucidate the function and mechanism of the Rv2741 gene in host-pathogen interactions.
  • To understand how Rv2741 contributes to the virulence of Mycobacterium tuberculosis.
  • To explore Rv2741's impact on host immune responses, specifically macrophage behavior.

Main Methods:

  • Generated recombinant Mycobacterium smegmatis (M. smegmatis) expressing the M. tuberculosis Rv2741 gene.
  • Analyzed the modulation of host immune mediators, including IL-1α and nitric oxide (NO).
  • Investigated the involvement of the MAPK signaling pathway (p38 and ERK1/2) and its effect on macrophage autophagy and apoptosis.

Main Results:

  • Rv2741 was found to downregulate IL-1α secretion, a key mediator of host response.
  • Rv2741 inhibited the p38 and ERK1/2 pathways within the MAPK signaling cascade.
  • Macrophage autophagy and apoptosis were suppressed, leading to altered cytokine profiles and reduced NO production, favoring M. smegmatis survival.

Conclusions:

  • Rv2741 acts as a multifunctional virulence factor for M. tuberculosis.
  • Rv2741 plays a critical role in immune evasion by modulating host inflammatory responses.
  • Understanding Rv2741's mechanisms enhances knowledge of M. tuberculosis pathogenesis and potential therapeutic targets.
Keywords:
Mycobacterium tuberculosisNOPE_PGRS familyRv2741apoptosis

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