Plasticity of antimicrobial and phagocytic programs in human macrophages.
IMMUNOLOGY(2019)
摘要
Macrophage (M phi) 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 M phi) have enhanced antimicrobial activity, whereas IL-10-derived alternatively activated macrophages (M2 M phi) were highly phagocytic but lacked antimicrobial activity. Given that the ability to modulate M phi polarization from M2 M phi to M1 M phi may promote a more effective immune response to infection, we investigated the plasticity of these M phi programs. Addition of IL-10 to M1 M phi induced M2-like M phi, but IL-15 had little effect on M2 M phi. We determined the set of immune receptors that are present on M2 M phi, elucidating two candidates for inducing plasticity of M2 M phi, Toll-like receptor 1 (TLR1) and interferon gamma (IFN-gamma) receptor 1. Stimulation of M2 M phi with TLR2/1 ligand (TLR2/1L) or IFN-gamma alone was not sufficient to alter M2 M phi phenotype or function. However, co-addition of TLR2/1L and IFN-gamma re-educated M2 M phi towards the M1 M phi 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 M phi maintained in polarizing conditions. Similarly, treatment of M2 M phi with both TLR2/1L and anti-IL-10 neutralizing antibodies led to polarization to the M1-like M phi phenotype and function. Together, our data demonstrate an approach to induce M phi plasticity that provides the potential for re-educating M phi function in human mycobacterial disease to promote host defense and limit pathogenesis.
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关键词
antimicrobial,macrophage,mycobacteria,phagocytosis,polarization
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