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Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
Monocytes infected with Mycobacterium tuberculosis regulate MAP kinase-dependent astrocyte MMP-9 secretion
James E Harris1, Justin A Green, Paul T Elkington
1Department of Infectious Diseases and Immunity, Imperial College, Hammersmith Campus, London, UK.
Journal of Leukocyte Biology
|November 3, 2006
Summary
Tuberculosis of the CNS (CNS-TB) involves matrix metalloproteinase-9 (MMP-9) that degrades tissue. Mycobacterium tuberculosis-infected monocytes trigger astrocyte MMP-9 release via IL-1beta and MAPK signaling, contributing to CNS-TB pathology.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Central Nervous System Tuberculosis (CNS-TB) is a severe condition with high mortality.
- CNS-TB pathology involves extensive destruction of neural tissues and the blood-brain barrier.
- Matrix metalloproteinase-9 (MMP-9) contributes to tissue damage by degrading CNS matrix components.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling MMP-9 activity in CNS-TB.
- To elucidate the role of monocytes and astrocytes in MMP-9 secretion during CNS-TB.
Main Methods:
- Zymography, Western analysis, and transcription factor assays were employed.
- Investigated MMP-9 secretion from astrocytes stimulated with Mycobacterium tuberculosis-infected monocyte conditioned media (CoMTB).
- Assessed the involvement of cytokines (IL-1beta, TNF-alpha) and MAPK pathways (p38, Erk, Jnk) in MMP-9 regulation.
Main Results:
- CoMTB induced MMP-9 secretion from astrocytes.
- IL-1beta was identified as a necessary cytokine for this induction, signaling through MAPK pathways.
- AP-1 DNA-binding activity, particularly c-Jun, FosB, and JunB subunits, was upregulated by CoMTB.
Conclusions:
- Monocyte-derived cytokines, especially IL-1beta, play a critical role in regulating astrocyte MMP-9 secretion.
- The IL-1beta-MAPK signaling axis is crucial for inducing MMP-9 in CNS-TB.
- These findings highlight the importance of monocyte-cytokine networks in creating a matrix-degrading environment in CNS-TB.
