The Ubiquitin-Modifying Enzyme A20 Terminates C-Type Lectin Receptor Signals and Is a Suppressor of Host Defense against Systemic Fungal Infection.

Journal Article (Journal Article)

C-type lectin receptors (CLRs) play key roles in antifungal defense. CLR-induced NF-κB is central to CLR functions in immunity, and thus, molecules that control the amplitude of CLR-induced NF-κB could profoundly influence host defense against fungal pathogens. However, little is known about the mechanisms that negatively regulate CLR-induced NF-κB, 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-κB 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.

Full Text

Duke Authors

Cited Authors

  • Liang, J; Zhang, JJ; Huang, H-I; Kanayama, M; Youssef, N; Jin, YJ; Reyes, EY; Abram, CL; Yang, S; Lowell, CA; Wang, D; Shao, L; Shinohara, ML; Zhang, JY; Hammer, GE

Published Date

  • August 19, 2020

Published In

Volume / Issue

  • 88 / 9

PubMed ID

  • 32540868

Pubmed Central ID

  • PMC7440764

Electronic International Standard Serial Number (EISSN)

  • 1098-5522

Digital Object Identifier (DOI)

  • 10.1128/IAI.00048-20


  • eng

Conference Location

  • United States