title: Proteomic characterization of human proinflammatory M1 and anti-inflammatory M2 macrophages and their response to Candida albicans.
abstract: In response to different stimuli, macrophages can differentiate into either a pro-inflammatory subtype (M1, classically activated macrophages) or acquire an anti-inflammatory phenotype (M2, alternatively activated macrophages). Candida albicans is the most important opportunistic fungus in nosocomial infections, and it is contended by neutrophils and macrophages during the first steps of the invasive infection. Murine macrophages responses to C. albicans have been widely studied, whereas the responses of human-polarized macrophages remain less characterized. In this study, we have characterized the proteomic differences between human M1- and M2-polarized macrophages, both in basal conditions and in response to C. albicans, by quantitative proteomics (2DE). This proteomic approach allowed us to identify metabolic routes and cytoskeletal rearrangement components that are the most relevant differences between M1 and M2 macrophages. The analysis has revealed fructose-1,6-bisphosphatase 1, a critical enzyme in gluconeogenesis, up-regulated in M1, as a novel protein marker for macrophage polarization. Regarding the response to C. albicans, an M1-to-M2 switch in polarization was observed. This M1-to-M2 switch might contribute to Candida pathogenicity by decreasing the generation of specific immune responses, thus enhancing fungal survival and colonization, or instead, may be part of the host attempt to reduce the inflammation and limit the damage of the infection.
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain; Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Madrid, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Reales-Calderón
authors.forename: Noemí
authors.initials: N
authors.lastname: Aguilera-Montilla
authors.forename: Ángel Luis
authors.initials: ÁL
authors.lastname: Corbí
authors.forename: Gloria
authors.initials: G
authors.lastname: Molero
authors.forename: Concha
authors.initials: C
authors.lastname: Gil
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D002176:Candida albicans / Q000378:metabolism* / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D008856:Microscopy, Fluorescence; D010587:Phagocytosis; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D012333:RNA, Messenger
keywords: Candida albicans; Fructose-1,6-bisphosphatase; Macrophage polarization; Metabolism; Microbiology; Two-dimensional difference in-gel electrophoresis