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Updated: Aug 24, 2026
Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to
Frank A W Verreck1, Tjitske de Boer, Dennis M L Langenberg
1Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Albinusdreef 2, NL-2333-ZA, Leiden, The Netherlands. verreck@bprc.nl
Abstract:
Macrophages (Mphi) play a central role as effector cells in immunity to intracellular pathogens such as Mycobacterium. Paradoxically, they also provide a habitat for intracellular bacterial survival. This paradoxical role of Mphi remains poorly understood. Here we report that this dual role may emanate from the functional plasticity of Mphi: Whereas Mphi-1 polarized in the presence of granulocyte-Mphi colony-stimulating factor promoted type 1 immunity, Mphi-2 polarized with Mphi colony-stimulating factor subverted type 1 immunity and thus may promote immune escape and chronic infection. Importantly, Mphi-1 secreted high levels of IL-23 (p40/p19) but no IL-12 (p40/p35) after (myco)bacterial activation. In contrast, activated Mphi-2 produced neither IL-23 nor IL-12 but predominantly secreted IL-10. Mphi-1 required IFN-gamma as a secondary signal to induce IL-12p35 gene transcription and IL-12 secretion. Activated dendritic cells produced both IL-12 and IL-23, but unlike Mphi-1 they slightly reduced their IL-23 secretion after addition of IFN-gamma. Binding, uptake, and outgrowth of a mycobacterial reporter strain was supported by both Mphi subsets, but more efficiently by Mphi-2 than Mphi-1. Whereas Mphi-1 efficiently stimulated type 1 helper cells, Mphi-2 only poorly supported type 1 helper function. Accordingly, activated Mphi-2 but not Mphi-1 down-modulated their antigen-presenting and costimulatory molecules (HLA-DR, CD86, and CD40). These findings indicate that (i) Mphi-1 and Mphi-2 play opposing roles in cellular immunity and (ii) IL-23 rather than IL-12 is the primary type 1 cytokine produced by activated proinflammatory Mphi-1. Mphi heterogeneity thus may be an important determinant of immunity and disease outcome in intracellular bacterial infection.
Insights
Macrophages exhibit a dual role in immunity, either fighting or harboring intracellular pathogens like Mycobacterium. This study reveals two distinct macrophage (Mphi) types: Mphi-1 promotes immunity, while Mphi-2 aids bacterial survival.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Macrophages (Mphi) are crucial in immunity against intracellular pathogens but can also harbor them.
- The paradoxical role of Mphi in host defense and pathogen survival is poorly understood.
- Mphi functional plasticity may explain their dual role in immunity.
Purpose of the Study:
- To investigate the functional plasticity of Mphi in the context of intracellular bacterial infections.
- To differentiate the roles of distinct Mphi subsets in type 1 immunity and pathogen control.
- To elucidate the cytokine profiles and immune regulatory functions of Mphi subsets.
Main Methods:
- Polarization of Mphi subsets (Mphi-1 and Mphi-2) using specific colony-stimulating factors.
- Activation of Mphi subsets with a mycobacterial reporter strain.
- Analysis of cytokine secretion (IL-23, IL-12, IL-10) and gene transcription.
- Assessment of Mphi antigen-presenting and costimulatory molecule expression.
- Evaluation of Mphi-1 and Mphi-2 support for type 1 helper cell function.
Main Results:
- Mphi-1, polarized with granulocyte-Mphi colony-stimulating factor, promoted type 1 immunity and secreted IL-23 upon activation.
- Mphi-2, polarized with Mphi colony-stimulating factor, subverted type 1 immunity, predominantly secreting IL-10.
- Mphi-1 required IFN-gamma for IL-12 secretion, while Mphi-2 produced neither IL-12 nor IL-23.
- Both Mphi subsets supported mycobacterial growth, with Mphi-2 being more efficient.
- Mphi-1 supported type 1 helper cells, whereas Mphi-2 down-modulated antigen-presenting and costimulatory molecules.
Conclusions:
- Mphi subsets (Mphi-1 and Mphi-2) exhibit opposing roles in cellular immunity against intracellular pathogens.
- IL-23, not IL-12, is the primary type 1 cytokine produced by activated proinflammatory Mphi-1.
- Mphi heterogeneity significantly influences immunity and disease outcomes in intracellular bacterial infections.
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