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Updated: Sep 20, 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 avium subsp. paratuberculosis exploits miRNA expression to modulate lipid metabolism and macrophage
Kathryn Wright1, Rachel Mizzi1, Karren M Plain1
1Sydney School of Veterinary Science, The University of Sydney, Faculty of Science, Sydney, NSW, Australia.
Abstract:
Pathogenic mycobacteria including Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne's disease, manipulate host macrophages to persist and cause disease. In mycobacterial infection, highly plastic macrophages, shift between inflammatory M1 and permissive M2 phenotypes which alter the disease outcome and allow bacteria to survive intracellularly. Here we examine the impact of MAP infection on polarised macrophages and how increased lipid availability alters macrophage phenotype and bacterial persistence. Further, we assess if host microRNA (miRNA) are sensitive to macrophage polarisation state and how MAP can drive their expression to overcome innate responses. Using in vitro MAP infection, we find that increasing lipid availability through supplementing culture media with exogenous lipid increases cellular nitric oxide production. Lipid-associated miRs -19a, -129, -24, and -24-3p are differentially expressed following macrophage polarisation and lipid supplementation and are further regulated during MAP infection. Collectively, our results highlight the importance of host lipid metabolism in MAP infection and demonstrate control of miRNA expression by MAP to favour intracellular persistence.
Insights
Mycobacterium avium subsp. paratuberculosis (MAP) manipulates host macrophages by altering lipid metabolism and microRNA (miRNA) expression to enhance its persistence and cause Johne
Area of Science:
- Immunology
- Microbiology
- Host-pathogen interactions
Background:
- Pathogenic mycobacteria, including Mycobacterium avium subsp. paratuberculosis (MAP), manipulate host macrophages for survival and disease progression.
- Macrophages exhibit plasticity, shifting between M1 (inflammatory) and M2 (permissive) phenotypes, influencing disease outcome and intracellular bacterial survival.
Purpose of the Study:
- To investigate the impact of MAP infection on polarized macrophages.
- To determine how increased lipid availability affects macrophage phenotype and MAP persistence.
- To assess host microRNA (miRNA) regulation by macrophage polarization and MAP infection.
Main Methods:
- In vitro infection of macrophages with MAP.
- Supplementation of culture media with exogenous lipids.
- Analysis of macrophage polarization states.
- Quantification of nitric oxide production.
- Differential expression analysis of specific microRNAs (miRs -19a, -129, -24, and -24-3p).
Main Results:
- Increased lipid availability enhanced nitric oxide production in macrophages.
- Specific lipid-associated miRNAs (-19a, -129, -24, -24-3p) showed differential expression upon macrophage polarization and lipid supplementation.
- MAP infection further regulated the expression of these miRNAs.
- MAP infection alters macrophage phenotype and promotes intracellular persistence.
Conclusions:
- Host lipid metabolism plays a crucial role in MAP infection dynamics.
- MAP actively controls host miRNA expression to facilitate its intracellular survival and persistence.
- Understanding these mechanisms can inform strategies against Johne's disease.
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