RT Journal Article
T1 Candida albicans induces pro-inflammatory and anti-apoptotic signals in macrophages as revealed by quantitative proteomics and phosphoproteomics
A1 Reales Calderón, José Antonio
A1 Sylvester, Marc
A1 Strijbis, Karin
A1 Jensen, Ole N.
A1 Nombela, César
A1 Gil, Concha
A1 Molero Martín-Portugués, María Gloria
AB Macrophages play a pivotal role in the prevention of Candida albicans infections. Yeast recognition and phagocytosis by macrophages is mediated by Pattern Recognition Receptors (PRRs) that initiate downstream signal transduction cascades by protein phosphorylation and dephosphorylation. We exposed RAW 264.7 macrophages to C. albicans for 3h and used SILAC to quantify macrophage proteins and phosphoproteins by mass spectrometry to study the effects of infection. We identified 53 macrophage up-regulated proteins and 15 less abundant in the presence of C. albicans out of a total of 2071 identified proteins. 922 unique protein phosphorylation sites were identified by phosphopeptide enrichment and mass spectrometry, including 327 previously unidentified mouse protein phosphorylation sites. 126 peptides showed an increase and 70 a decrease in their phosphorylation level. The majority of the differentially expressed and phosphorylated proteins are receptors, mitochondrial ribosomal proteins, cytoskeletal proteins, and transcription factor activators involved in inflammatory and oxidative responses. In addition, we identified 22 proteins and phosphoproteins related to apoptosis. The analysis of apoptotic markers revealed that anti-apoptotic signals prevailed during the interaction of the yeast. Our proteomics study suggests that besides inflammation, apoptosis is a central pathway in the immune defense against C. albicans infection.BIOLOGICAL SIGNIFICANCE:This work uses SILAC and SIMAC methodology combined with CPP (+ TiO2) to study protein and phosphopeptide changes in RAW 264.7 macrophages in response to coincubation with Candida albicans for 3h. We show that the presence of C. albicans induces inflammatory responses and inhibits apoptosis in the macrophages. Our phosphoproteomic analysis identified 327 new mouse protein phosphorylation sites.
PB Elsevier
SN 1874-3919
YR 2013
FD 2013-07-05
LK https://hdl.handle.net/20.500.14352/34908
UL https://hdl.handle.net/20.500.14352/34908
LA eng
NO Reales-Calderón JA, Sylvester M, Strijbis K, Jensen ON, Nombela C, Molero G, et al. Candida albicans induces pro-inflammatory and anti-apoptotic signals in macrophages as revealed by quantitative proteomics and phosphoproteomics. Journal of Proteomics 2013;91:106–35. https://doi.org/10.1016/j.jprot.2013.06.026.
NO This work was supported by BIO 2009-07654 and BIO 2012-31767 from the Ministerio de Economía y Competitividad, PROMT (S2010/BMD-2414) from the Comunidad Autónoma de Madrid, and REIPI, Spanish Network for the Research in Infectious Diseases (RD06/0008/1027 and RD12/0015/0004) from the ISCIII; and the Banco Santander Central HispanoUniversidad Complutense Research Group (UCM-920685). Dr. C. Nombela is the director of the Special Chair in Genomics and Proteomics.
NO Ministerio de Economía y Competitividad (Epaña)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III 
NO Spanish Network for the Research in Infectious Diseases
NO Universidad Complutense de Madrid 
NO Banco Santader
DS Docta Complutense
RD 18 mar 2026