Research paperHuman macrophages chronically exposed to LPS can be reactivated by stimulation with MDP to acquire an antimicrobial phenotype

- Macrophages chronically exposed to LPS behave similar to tolerized macrophages.
- Muramyl dipeptide plus LPS induce M1-M2 mix phenotype in Macrophages chronically exposed to LPS.
- Muramyl dipeptide plus LPS reestablish TNFα production in Macrophages chronically exposed to LPS.

Macrophages are important in host defense and can differentiate into functionally distinct subsets named classically (M1) or alternatively (M2) activated. In several inflammatory disorders, macrophages become tolerized to prevent deleterious consequences. This tolerization reduces the ability of macrophages to respond to bacterial components (e.g., LPS) maintaining a low level of inflammation but compromising the ability of macrophages to mount an effective immune response during subsequent pathogen encounters.In this study, we aimed to reactivate human monocyte-derived macrophages chronically exposed to LPS by re-stimulation with muramyl dipeptide (MDP). We observed an undefined profile of cell surface marker expression during endotoxin tolerance and absence of TNFα production. Stimulating macrophages chronically exposed to LPS with LPS + MDP restored TNFα, production together with an increased production of IL1, IL6, IFNγ, IL4, IL5 and IL10. These results suggest that macrophages chronically exposed to LPS possess a mixed M1-M2 phenotype with sufficient antimicrobial and homeostatic potential.