title: Candida albicans Modifies the Protein Composition and Size Distribution of THP-1 Macrophage-Derived Extracellular Vesicles.
abstract: The effectiveness of macrophages in the response to systemic candidiasis is crucial to an effective clearance of the pathogen. The secretion of proteins, mRNAs, noncoding RNAs and lipids through extracellular vesicles (EVs) is one of the mechanisms of communication between immune cells. EVs change their cargo to mediate different responses, and may play a role in the response against infections. Thus we have undertaken the first quantitative proteomic analysis on the protein composition of THP-1 macrophage-derived EVs during the interaction with Candida albicans. This study revealed changes in EVs sizes and in protein composition, and allowed the identification and quantification of 717 proteins. Of them, 133 proteins changed their abundance due to the interaction. The differentially abundant proteins were involved in functions relating to immune response, signaling, or cytoskeletal reorganization. THP-1-derived EVs, both from control and from Candida-infected macrophages, had similar effector functions on other THP-1-differenciated macrophages, activating ERK and p38 kinases, and increasing both the secretion of proinflammatory cytokines and the candidacidal activity; while in THP-1 nondifferenciated monocytes, only EVs from infected macrophages increased significantly the TNF-α secretion. Our findings provide new information on the role of macrophage-derived EVs in response to C. albicans infection and in macrophages communication.
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid Plaza de Ramón y Cajal s/n , Madrid 28040, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Madrid 28034, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Reales-Calderón
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid Plaza de Ramón y Cajal s/n , Madrid 28040, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Madrid 28034, Spain.
authors.forename: Catarina
authors.initials: C
authors.lastname: Vaz
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid Plaza de Ramón y Cajal s/n , Madrid 28040, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Madrid 28034, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Monteoliva
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid Plaza de Ramón y Cajal s/n , Madrid 28040, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Madrid 28034, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Molero
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid Plaza de Ramón y Cajal s/n , Madrid 28040, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Madrid 28034, Spain.
authors.forename: Concha
authors.initials: C
authors.lastname: Gil
mesh_terms: D002176:Candida albicans / Q000254:growth & development / Q000472:pathogenicity*; D002454:Cell Differentiation; D002460:Cell Line; D019295:Computational Biology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003599:Cytoskeleton / Q000276:immunology / Q000382:microbiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology; D000067128:Extracellular Vesicles / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000276:immunology; D063990:Gene Ontology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D058977:Molecular Sequence Annotation; D020543:Proteome / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D020543:Proteome; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Candida albicans; extracellular vesicles; immune response; inflammation; macrophages; tandem mass tagging