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Updated: Nov 6, 2025
Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
Mycobacterium tuberculosis effector PPE36 attenuates host cytokine storm damage via inhibiting macrophage M1
Zhen Gong1, Shuang Han1, Tian Liang1
1State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, Chongqing, China.
Abstract:
Tuberculosis caused by Mycobacterium tuberculosis remains a serious global public health threat. Macrophage polarization is crucial for the innate immunity against M. tuberculosis. However, how M. tuberculosis interferes with macrophage polarization is elusive. We demonstrated here that M. tuberculosis PPE36 (Rv2108) blocked macrophage M1 polarization, preventing the cytokine storm, and alleviating inflammatory damage to mouse immune organs. PPE36 inhibited the polarization of THP-1 cell differentiation to M1 macrophages, reduced mitochondrial dehydrogenase activity, inhibited the expression of CD16, and repressed the expression of pro-inflammatory cytokines IL-6 and TNF-α, as well as chemokines CXCL9, CXCL10, CCL3, and CCL5. Intriguingly, in the mouse infection model, PPE36 significantly alleviated the inflammatory damage of immune organs caused by a cytokine storm. Furthermore, we found that PPE36 inhibited the polarization of macrophages into mature M1 macrophages by suppressing the ERK signaling. The study provided novel insights into the function and mechanism of action of M. tuberculosis effector PPE36 both at the cellular and animal level.
Insights
Mycobacterium tuberculosis PPE36 protein blocks M1 macrophage polarization, reducing inflammation and immune organ damage. This finding offers new insights into tuberculosis pathogenesis and potential therapeutic targets.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major global health concern.
- Macrophage polarization is critical for controlling M. tuberculosis infection.
- The mechanisms by which M. tuberculosis manipulates macrophage polarization remain largely unknown.
Purpose of the Study:
- To investigate the role of M. tuberculosis PPE36 (Rv2108) in modulating macrophage polarization.
- To elucidate the molecular mechanisms underlying PPE36's function.
- To assess the impact of PPE36 on host immune responses and organ damage in a mouse model.
Main Methods:
- Utilized THP-1 cell differentiation to study M1 macrophage polarization.
- Assessed mitochondrial dehydrogenase activity and expression of key M1 markers (CD16, IL-6, TNF-α, CXCL9, CXCL10, CCL3, CCL5).
- Employed a mouse infection model to evaluate PPE36's effect on immune organ inflammation and cytokine storm.
- Investigated the involvement of the ERK signaling pathway.
Main Results:
- M. tuberculosis PPE36 significantly inhibited THP-1 cell differentiation into M1 macrophages.
- PPE36 suppressed M1-associated markers, including CD16, IL-6, TNF-α, and various chemokines.
- In vivo, PPE36 alleviated inflammatory damage in mouse immune organs caused by a cytokine storm.
- The study identified PPE36's inhibition of M1 polarization via suppression of the ERK signaling pathway.
Conclusions:
- M. tuberculosis PPE36 acts as an effector protein that hinders M1 macrophage polarization.
- PPE36 mitigates the detrimental effects of a cytokine storm, reducing inflammatory damage.
- The findings reveal a novel mechanism of immune evasion by M. tuberculosis involving PPE36 and the ERK pathway, offering potential therapeutic avenues.
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