دورية أكاديمية
Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity
| العنوان: | Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity |
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| المؤلفون: | Dayanira Alsina‐Beauchamp, Alejandra Escós, Pilar Fajardo, Diego González‐Romero, Ester Díaz‐Mora, Ana Risco, Miguel A Martín‐Serrano, Carlos delFresno, Jorge Dominguez‐Andrés, Noelia Aparicio, Rafal Zur, Natalia Shpiro, Gordon D Brown, Carlos Ardavín, Mihai G Netea, Susana Alemany, Juan J Sanz‐Ezquerro, Ana Cuenda |
| المصدر: | EMBO Molecular Medicine, Vol 10, Iss 5, Pp n/a-n/a (2018) |
| بيانات النشر: | Springer Nature, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | Candida albicans, infection, kinase inhibitor, p38MAPK, signalling, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract 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 p38γ and p38δ 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 p38γ/p38δ. In mice, p38γ/p38δ 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 p38γ/δ‐null mice, reducing septic shock. p38γ/p38δ in myeloid cells are critical for this effect. Moreover, pharmacological inhibition of p38γ/p38δ in mice reduces fungal burden, revealing that these p38MAPKs may be therapeutic targets for treating C. albicans infection in humans. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
| DOI: | 10.15252/emmm.201708485 |
| URL الوصول: | https://doaj.org/article/939e61b85a3b4a58b2f2dc2991a14ffb |
| رقم الأكسشن: | edsdoj.939e61b85a3b4a58b2f2dc2991a14ffb |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.201708485 |