Related Experiment Video
Updated: Feb 3, 2026
Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro
Published on: January 25, 2017
Plasticity of antimicrobial and phagocytic programs in human macrophages
Dennis Montoya1, Manali Mehta2, Benjamin G Ferguson3
1Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA, USA.
Abstract:
Macrophage (MΦ) polarization is triggered during the innate immune response to defend against microbial pathogens, but can also contribute to disease pathogenesis. In a previous study, we found that interleukin-15 (IL-15) -derived classically activated macrophages (M1 MΦ) have enhanced antimicrobial activity, whereas IL-10-derived alternatively activated macrophages (M2 MΦ) were highly phagocytic but lacked antimicrobial activity. Given that the ability to modulate MΦ polarization from M2 MΦ to M1 MΦ may promote a more effective immune response to infection, we investigated the plasticity of these MΦ programs. Addition of IL-10 to M1 MΦ induced M2-like MΦ, but IL-15 had little effect on M2 MΦ. We determined the set of immune receptors that are present on M2 MΦ, elucidating two candidates for inducing plasticity of M2 MΦ, Toll-like receptor 1 (TLR1) and interferonγ (IFN-γ) receptor 1. Stimulation of M2 MΦ with TLR2/1 ligand (TLR2/1L) or IFN-γ alone was not sufficient to alter M2 MΦ phenotype or function. However, co-addition of TLR2/1L and IFN-γ re-educated M2 MΦ towards the M1 MΦ phenotype, with a decrease in the phagocytosis of lipids and mycobacteria, as well as recovery of the vitamin-D-dependent antimicrobial pathway compared with M2 MΦ maintained in polarizing conditions. Similarly, treatment of M2 MΦ with both TLR2/1L and anti-IL-10 neutralizing antibodies led to polarization to the M1-like MΦ phenotype and function. Together, our data demonstrate an approach to induce MΦ plasticity that provides the potential for re-educating MΦ function in human mycobacterial disease to promote host defense and limit pathogenesis.
Insights
Researchers found a way to re-educate alternatively activated macrophages (M2 MΦ) to become classically activated macrophages (M1 MΦ). This macrophage plasticity enhances antimicrobial activity, offering potential for treating mycobacterial diseases.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophage (MΦ) polarization is crucial for innate immunity and disease pathogenesis.
- Classically activated M1 MΦ exhibit enhanced antimicrobial activity, while alternatively activated M2 MΦ are phagocytic but lack antimicrobial function.
- Modulating MΦ polarization from M2 to M1 could improve immune responses to infection.
Purpose of the Study:
- To investigate the plasticity of MΦ polarization, specifically the ability to convert M2 MΦ to M1 MΦ.
- To identify immune receptors on M2 MΦ that can induce plasticity.
- To develop strategies for re-educating MΦ function in human mycobacterial diseases.
Main Methods:
- MΦ polarization was induced using interleukin-15 (IL-15) for M1 MΦ and interleukin-10 (IL-10) for M2 MΦ.
- M2 MΦ were stimulated with Toll-like receptor 1 (TLR1) and interferon-γ (IFN-γ) receptor 1 ligands and IFN-γ.
- MΦ phenotype and function were assessed by measuring lipid and mycobacteria phagocytosis and vitamin-D-dependent antimicrobial pathways.
Main Results:
- IL-10 induced M2-like MΦ from M1 MΦ, but IL-15 had minimal effect on M2 MΦ.
- Co-stimulation of M2 MΦ with a TLR2/1 ligand (TLR2/1L) and IFN-γ re-educated them towards an M1 phenotype.
- This re-education decreased lipid and mycobacteria phagocytosis and restored antimicrobial function.
- Treatment with TLR2/1L and anti-IL-10 neutralizing antibodies also induced M1-like MΦ phenotype and function.
Conclusions:
- MΦ plasticity can be induced by co-stimulating M2 MΦ with TLR2/1L and IFN-γ or TLR2/1L and anti-IL-10 antibodies.
- This approach converts M2 MΦ to an M1-like phenotype with restored antimicrobial activity.
- The findings offer a potential strategy for re-educating MΦ in human mycobacterial diseases to enhance host defense.
Related Concept Videos
00:58Plasticity
01:31Plasticizers
Plasticizers function by using surface-active agents to create repulsive electrostatic forces between cement particles. This dispersion enhances the concrete's...
01:28Antimicrobial Effectiveness
01:21Plastic Behavior
01:14Plastic Deformations
01:19Plastic Deformations