2026-04-27T08:02:39Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/66732025-04-03T13:14:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Alsina-Beauchamp, Dayanira
author
Escos, Alejandra
author
Fajardo, Pilar
author
Gonzalez-Romero, Diego
author
Diaz-Mora, Ester
author
Risco, Ana
author
Martin-Serrano, Miguel A.
author
del Fresno, Carlos
author
Domínguez-Andrés, Jorge
author
Aparicio, Noelia
author
Zur, Rafal
author
Shpiro, Natalia
author
Brown, Gordon D.
author
Ardavín, Carlos
author
Netea, Mihai G
author
Alemany, Susana
author
Sanz-Ezquerro, Juan J.
author
Cuenda, Ana
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación La Marató TV3
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Dutch Research Council (Holanda)
funder
Wellcome Trust
funder
Medical Research Council (Reino Unido)
2018-11-22T08:10:51Z
2018-11-22T08:10:51Z
2018
EMBO Mol Med. 2018; 10(5):e8485
1757-4676
http://hdl.handle.net/20.500.12105/6673
29661910
10.15252/emmm.201708485
1757-4684
EMBO Molecular Medicine
Candida albicans is a frequent aetiologic agent of sepsis associated with high mortality in immunocompromised patients. Developing new antifungal therapies is a medical need due to the low efficiency and resistance to current antifungal drugs. Here, we show that p38 gamma and p38 delta regulate the innate immune response to C.albicans. We describe a new TAK1-TPL2-MKK1-ERK1/2 pathway in macrophages, which is activated by Dectin-1 engagement and positively regulated by p38 gamma/p38 delta. In mice, p38 gamma/p38 delta deficiency protects against C.albicans infection by increasing ROS and iNOS production and thus the antifungal capacity of neutrophils and macrophages, and by decreasing the hyper-inflammation that leads to severe host damage. Leucocyte recruitment to infected kidneys and production of inflammatory mediators are decreased in p38 beta/delta-null mice, reducing septic shock. p38 gamma/p38 delta in myeloid cells are critical for this effect. Moreover, pharmacological inhibition of p38 gamma/p38 delta in mice reduces fungal burden, revealing that these p38MAPKs may be therapeutic targets for treating C. albicans infection in humans.
eng
Candida albicans
Infection
Kinase inhibitor
p38MAPK
Signalling
PATTERN-RECOGNITION RECEPTORS
TNF-ALPHA PRODUCTION
LOCI-2 TPL2 KINASE
INNATE IMMUNITY
IN-VIVO
INVASIVE CANDIDIASIS
CROSS-TALK
INFLAMMATION
P38-GAMMA
P38-DELTA
Myeloid cell deficiency of p38 gamma/p38 delta protects against candidiasis and regulates antifungal immunity
journal article
URL
https://repisalud.isciii.es/bitstreams/708c97e9-625b-44f3-837c-f5f1ea139a97/download
File
MD5
131c3a6c044e7fe94408ed734da93dfb
2183688
application/pdf
MyeloidCellDeficiency_2018.pdf
URL
https://repisalud.isciii.es/bitstreams/63d6be65-7c6b-47af-b716-8a897a7eeb85/download
File
MD5
a5f8ef8642369f15baf89e1f2d795df1
73021
text/plain
MyeloidCellDeficiency_2018.pdf.txt