2026-04-27T08:02:39Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/66732025-04-03T13:14:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2018 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. 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 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