| First Author | Liang J | Year | 2020 |
| Journal | Infect Immun | Volume | 88 |
| Issue | 9 | PubMed ID | 32540868 |
| Mgi Jnum | J:304231 | Mgi Id | MGI:6694439 |
| Doi | 10.1128/IAI.00048-20 | Citation | Liang J, et al. (2020) The Ubiquitin-Modifying Enzyme A20 Terminates C-Type Lectin Receptor Signals and Is a Suppressor of Host Defense against Systemic Fungal Infection. Infect Immun 88(9) |
| abstractText | C-type lectin receptors (CLRs) play key roles in antifungal defense. CLR-induced NF-kappaB is central to CLR functions in immunity, and thus, molecules that control the amplitude of CLR-induced NF-kappaB could profoundly influence host defense against fungal pathogens. However, little is known about the mechanisms that negatively regulate CLR-induced NF-kappaB, and molecules which act on the CLR family broadly and which directly regulate acute CLR-signaling cascades remain unidentified. Here, we identify the ubiquitin-editing enzyme A20 as a negative regulator of acute NF-kappaB activation downstream of multiple CLR pathways. Absence of A20 suppression results in exaggerated CLR responses in cells which are A20 deficient and also cells which are A20 haplosufficient, including multiple primary immune cells. Loss of a single allele of A20 results in enhanced defense against systemic Candida albicans infection and prolonged host survival. Thus, A20 restricts CLR-induced innate immune responses in vivo and is a suppressor of host defense against systemic fungal infection. |
