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InsP3R-SEC5 interaction on phagosomes modulates innate immunity to Candida albicans by promoting cytosolic Ca2+ elevation and TBK1 activity

Overview of attention for article published in BMC Biology, April 2018
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Title
InsP3R-SEC5 interaction on phagosomes modulates innate immunity to Candida albicans by promoting cytosolic Ca2+ elevation and TBK1 activity
Published in
BMC Biology, April 2018
DOI 10.1186/s12915-018-0507-6
Pubmed ID
Authors

Long Yang, Wenwen Gu, King-Ho Cheung, Lan Yan, Benjamin Chun-Kit Tong, Yuanying Jiang, Jun Yang

Abstract

Candida albicans (C. albicans) invasion triggers antifungal innate immunity, and the elevation of cytoplasmic Ca2+ levels via the inositol 1,4,5-trisphosphate receptor (InsP3R) plays a critical role in this process. However, the molecular pathways linking the InsP3R-mediated increase in Ca2+ and immune responses remain elusive. In the present study, we find that during C. albicans phagocytosis in macrophages, exocyst complex component 2 (SEC5) promotes InsP3R channel activity by binding to its C-terminal α-helix (H1), increasing cytosolic Ca2+ concentrations ([Ca2+]c). Immunofluorescence reveals enriched InsP3R-SEC5 complex formation on phagosomes, while disruption of the InsP3R-SEC5 interaction by recombinant H1 peptides attenuates the InsP3R-mediated Ca2+ elevation, leading to impaired phagocytosis. Furthermore, we show that C. albicans infection promotes the recruitment of Tank-binding kinase 1 (TBK1) by the InsP3R-SEC5 interacting complex, leading to the activation of TBK1. Subsequently, activated TBK1 phosphorylates interferon regulatory factor 3 (IRF-3) and mediates type I interferon responses, suggesting that the InsP3R-SEC5 interaction may regulate antifungal innate immune responses not only by elevating cytoplasmic Ca2+ but also by activating the TBK1-IRF-3 pathway. Our data have revealed an important role of the InsP3R-SEC5 interaction in innate immune responses against C. albicans.

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The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 3 17%
Student > Bachelor 2 11%
Researcher 2 11%
Lecturer 1 6%
Professor 1 6%
Other 4 22%
Unknown 5 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 22%
Medicine and Dentistry 3 17%
Immunology and Microbiology 3 17%
Agricultural and Biological Sciences 2 11%
Unknown 6 33%