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Updated: Jun 5, 2026
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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
CMPK2 restricts Mycobacterium tuberculosis replication and regulates macrophage gene expression.
John Neff1, Victoria A Ektnitphong1, Priscila C Campos1
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
Biorxiv : the Preprint Server for Biology
|June 4, 2026
Summary
The mitochondrial enzyme CMPK2 limits Mycobacterium tuberculosis replication in human macrophages by regulating immune gene expression. Its role in host defense against Mtb is context-dependent, showing importance in human cells but not in mouse models.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Host cell metabolism significantly impacts innate immunity against intracellular pathogens.
- The specific role of nucleotide metabolism in antimicrobial defense is not fully understood.
Purpose of the Study:
- To investigate the role of mitochondrial nucleoside monophosphate kinase 2 (CMPK2) in macrophage response to Mycobacterium tuberculosis (Mtb).
- To identify CMPK2 as a potential regulator of innate immunity against Mtb.
Main Methods:
- Targeted genetic screening of host factors in human macrophages infected with Mtb.
- Gene knockdown using shRNA and knockout using CRISPR-Cas9 to assess CMPK2 function.
- Transcriptomic profiling to analyze gene expression changes upon CMPK2 loss.
- In vivo studies using myeloid-specific Cmpk2 knockout mice.
Main Results:
- Depletion of CMPK2 led to increased Mtb replication in human macrophages.
- CMPK2 expression was upregulated upon macrophage activation and Mtb infection.
- Loss of CMPK2 altered gene expression, notably reducing innate immune and inflammatory responses.
- Myeloid-specific deletion of Cmpk2 in mice did not affect bacterial burden or survival.
Conclusions:
- CMPK2 acts as a host factor that restricts Mtb replication in human macrophages.
- CMPK2 influences innate immune gene expression programs during Mtb infection.
- The contribution of CMPK2 to host defense against Mtb is context-dependent, differing between human cells and mouse models.
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