Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity
EMBO Molecular Medicine, Volume 10, No. 5, Article e8485, Year 2018
Notification
URL copied to clipboard!
Description
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. © 2018 The Authors. Published under the terms of the CC BY 4.0 license
Authors & Co-Authors
Escõs, Alejandra
Spain, Madrid
Csic - Centro Nacional de Biotecnologia Cnb
Domínguez-Andrés, Jorge
Spain, Madrid
Csic - Centro Nacional de Biotecnologia Cnb
Brown, Gordon D.A.
United Kingdom, London
Medical Research Council
Netea, Mihai Gheorghe
Netherlands, Nijmegen
Radboud University Medical Center
Alemany, Susana
Spain, Madrid
Universidad Autónoma de Madrid
Statistics
Citations: 17
Authors: 5
Affiliations: 5
Identifiers
Doi:
10.15252/emmm.201708485
ISSN:
17574676