Bibliographic Details
| Title: |
Disrupting the Dok3–Card9 Interaction with Synthetic Peptides Enhances Antifungal Effector Functions of Human Neutrophils |
| Authors: |
Jia Tong Loh, Joey Kay Hui Teo, Srinivasaraghavan Kannan, Chandra S. Verma, Hong-Hwa Lim, Kong-Peng Lam |
| Source: |
Pharmaceutics, Vol 15, Iss 7, p 1780 (2023) |
| Publisher Information: |
MDPI AG, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Pharmacy and materia medica |
| Subject Terms: |
neutrophils, antifungal immunity, Dok3, Card9, interference peptide, Pharmacy and materia medica, RS1-441 |
| More Details: |
Invasive fungal disease is an emerging and serious public health threat globally. The expanding population of susceptible individuals, together with the rapid emergence of multidrug-resistant fungi pathogens, call for the development of novel therapeutic strategies beyond the limited repertoire of licensed antifungal drugs. Card9 is a critical signaling molecule involved in antifungal defense; we have previously identified Dok3 to be a key negative regulator of Card9 activity in neutrophils. In this study, we identified two synthetic peptides derived from the coiled-coil domain of Card9, which can specifically block Dok3–Card9 binding. We showed that these peptides are cell-permeable, non-toxic, and can enhance antifungal cytokine production and the phagocytosis of human neutrophils upon fungal infection. Collectively, these data provide a proof of concept that disrupting the Dok3–Card9 interaction can boost the antifungal effector functions of neutrophils; they further suggest the potential utility of these peptide inhibitors as an immune-based therapeutic to fight fungal infection. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1999-4923 |
| Relation: |
https://www.mdpi.com/1999-4923/15/7/1780; https://doaj.org/toc/1999-4923 |
| DOI: |
10.3390/pharmaceutics15071780 |
| Access URL: |
https://doaj.org/article/77b5935a20fd4500a7a3b5e138363e74 |
| Accession Number: |
edsdoj.77b5935a20fd4500a7a3b5e138363e74 |
| Database: |
Directory of Open Access Journals |
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