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OTUD1 Regulates Antifungal Innate Immunity through Deubiquitination of CARD9

Xiaorong Chen1, Honghai Zhang1, Xueer Wang1

  • 1Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, 250012 Jinan, Shandong, People's Republic of China.

Journal of Immunology (Baltimore, Md. : 1950)
|April 1, 2021
PubMed

Insights

Ovarian tumor deubiquitinase 1 (OTUD1) regulates CARD9, a key protein in antifungal immunity. OTUD1 deubiquitinates CARD9, enhancing immune responses against fungal infections.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • CARD9 is a crucial adaptor protein in antifungal innate immunity.
  • Regulation of CARD9 activity by ubiquitination is vital, but involved deubiquitinases are not fully understood.

Purpose of the Study:

  • To identify and characterize the role of deubiquitinases in regulating CARD9 function.
  • To elucidate the mechanism by which OTUD1 impacts CARD9-mediated antifungal immunity.

Main Methods:

  • Co-immunoprecipitation to assess protein interactions.
  • In vitro deubiquitinase assays to determine OTUD1 activity on CARD9.
  • Analysis of NF-κB and MAPK signaling pathways.
  • Fungal infection models in wild-type and Otud1 knockout mice.

Main Results:

  • OTUD1 directly interacts with CARD9 and removes polyubiquitin chains.
  • OTUD1 deubiquitination activates CARD9, leading to NF-κB and MAPK pathway signaling.
  • OTUD1 deficiency compromises CARD9-mediated cytokine production and increases susceptibility to fungal infections in vivo.

Conclusions:

  • OTUD1 is a critical regulator of CARD9 signaling.
  • OTUD1 plays an essential role in antifungal innate immunity by deubiquitinating CARD9.

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