Enrichment of ATP Binding Proteins Unveils Proteomic Alterations in Human Macrophage Cell Death, Inflammatory Response, and Protein Synthesis after Interaction with Candida albicans

Macrophages are involved in the primary human response to Candida albicans. After pathogen recognition, signaling pathways are activated, leading to the production of cytokines, chemokines, and antimicrobial peptides. ATP binding proteins are crucial for this regulation. Here, a quantitative proteom...

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Bibliographic Details
Authors: Vaz, Catarina Oliveira, Reales Calderón, José Antonio, Pitarch Velasco, Aída, Vellosillo, Perceval, Trevisan Herraz, Marco, Hernáez Sánchez, Maria Luisa, Monteoliva Díaz, Lucía, Gil , Concha
Format: article
Publication Date:2019
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/13404
Online Access:https://hdl.handle.net/20.500.14352/13404
Access Level:Open access
Keyword:582.282:612.017
577.112
579
Macrophages
Candida albicans
Proteomics
SILAC
ATP binding proteins
Biología molecular (Biología)
Bioquímica (Biología)
Microbiología (Biología)
Microbiología (Farmacia)
2415 Biología Molecular
2302 Bioquímica
2414 Microbiología
3302.03 Microbiología Industrial
Description
Summary:Macrophages are involved in the primary human response to Candida albicans. After pathogen recognition, signaling pathways are activated, leading to the production of cytokines, chemokines, and antimicrobial peptides. ATP binding proteins are crucial for this regulation. Here, a quantitative proteomic and phosphoproteomic approach was carried out for the study of human macrophage ATP-binding proteins after interaction with C. albicans. From a total of 547 nonredundant quantified proteins, 137 were ATP binding proteins and 59 were detected as differentially abundant. From the differentially abundant ATP-binding proteins, 6 were kinases (MAP2K2, SYK, STK3, MAP3K2, NDKA, and SRPK1), most of them involved in signaling pathways. Furthermore, 85 phosphopeptides were quantified. Macrophage proteomic alterations including an increase of protein synthesis with a consistent decrease in proteolysis were observed. Besides, macrophages showed changes in proteins of endosomal trafficking together with mitochondrial proteins, including some involved in the response to oxidative stress. Regarding cell death mechanisms, an increase of antiapoptotic over pro-apoptotic signals is suggested. Furthermore, a high pro-inflammatory response was detected, together with no upregulation of key mi-RNAs involved in the negative feedback of this response. These findings illustrate a strategy to deepen the knowledge of the complex interactions between the host and the clinically important pathogen C. albicans.