Journal article
HECT E3 Ubiquitin Ligase Nedd4 Is Required for Antifungal Innate Immunity
The Journal of immunology (1950), Vol.207(3), pp.868-877
08/01/2021
DOI: 10.4049/jimmunol.2100083
PMCID: PMC8324540
PMID: 34282001
Abstract
Candida albicans is the most common cause of fungal infections in humans, and disseminated candidiasis has become one of the leading causes of hospital-acquired bloodstream infections with a high mortality rate. However, little is known about the host-pathogen interactions and the mechanisms of antifungal immunity. Here, we report that Nedd4 (neuronal precursor cell-expressed developmentally downregulated 4) is essential for signaling through Dectin-1 and Dectin-2/3. We showed that mice that lack Nedd4 globally or only in the myeloid compartment are highly susceptible to systemic C. albicans infection, which correlates with heightened organ fungal burden, defective inflammatory response, impaired leukocyte recruitment to the kidneys, and defective reactive oxygen species expression by granulocytes. At the molecular level, Nedd4-/- macrophages displayed impaired activation of TGF-β-activating kinase-1 and NF-κB, but normal activation of spleen tyrosine kinase and protein kinase C-δ on C. albicans yeast and hyphal infections. These data suggest that Nedd4 regulates signaling events downstream of protein kinase C-δ but upstream of or at TGF-β-activating kinase-1.
Details
- Title: Subtitle
- HECT E3 Ubiquitin Ligase Nedd4 Is Required for Antifungal Innate Immunity
- Creators
- Patrick K Nuro-Gyina - University of IowaNa Tang - University of IowaHui Guo - University of IowaChengkai Yan - University of IowaQiuming Zeng - University of IowaThomas J Waldschmidt - University of IowaJian Zhang - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.207(3), pp.868-877
- DOI
- 10.4049/jimmunol.2100083
- PMID
- 34282001
- PMCID
- PMC8324540
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R01 AI123253; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R01 AI123253-02S1
- Language
- English
- Date published
- 08/01/2021
- Academic Unit
- Pathology; Internal Medicine
- Record Identifier
- 9984186428402771
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