title: Human macrophages chronically exposed to LPS can be reactivated by stimulation with MDP to acquire an antimicrobial phenotype.
abstract: 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.
authors.affiliation: Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.
authors.forename: Silvia
authors.initials: S
authors.lastname: Guzmán-Beltrán
authors.affiliation: Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: Torres
authors.affiliation: Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.
authors.forename: Monserrat
authors.initials: M
authors.lastname: Arellano
authors.affiliation: Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico. Electronic address: ejuarez@iner.gob.mx.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Juárez
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000145:classification / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D009000:Monocytes / Q000166:cytology; D020102:Mycobacterium smegmatis / Q000254:growth & development; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C433788:lipopolysaccharide, E. coli O26-B6; D000119:Acetylmuramyl-Alanyl-Isoglutamine
keywords: LPS; MDP; Macrophage polarization