| First Author | Alsina-Beauchamp D | Year | 2018 |
| Journal | EMBO Mol Med | Volume | 10 |
| Issue | 5 | PubMed ID | 29661910 |
| Mgi Jnum | J:292417 | Mgi Id | MGI:6448888 |
| Doi | 10.15252/emmm.201708485 | Citation | Alsina-Beauchamp D, et al. (2018) Myeloid cell deficiency of p38gamma/p38delta protects against candidiasis and regulates antifungal immunity. EMBO Mol Med 10(5) |
| abstractText | 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 p38gamma and p38delta 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 p38gamma/p38delta. In mice, p38gamma/p38delta 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 p38gamma/delta-null mice, reducing septic shock. p38gamma/p38delta in myeloid cells are critical for this effect. Moreover, pharmacological inhibition of p38gamma/p38delta in mice reduces fungal burden, revealing that these p38MAPKs may be therapeutic targets for treating C. albicans infection in humans. |
