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The globular C1q receptor is required for epidermal growth factor receptor signaling during Candida albicans infection

Phan, Quynh T. and Lin, Jianfeng and Solis, Norma V. and Eng, Michael and Swidergall, Marc and Wang, Feng and Li, Shan and Gaffen, Sarah L. and Chou, Tsui-Fen and Filler, Scott G. (2021) The globular C1q receptor is required for epidermal growth factor receptor signaling during Candida albicans infection. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210528-084342141

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Abstract

During oropharyngeal candidiasis, Candida albicans activates the epidermal growth factor receptor (EGFR), which induces oral epithelial cells to both endocytose the fungus and synthesize proinflammatory mediators that orchestrate the host immune response. To elucidate the signaling pathways that are stimulated when C. albicans interacts with EGFR, we analyzed the proteins that associate with EGFR when C. albicans infects human oral epithelial cells. We identified 1214 proteins that were associated with EGFR in C. albicans-infected cells. We investigated the function of seven of these proteins that either showed increased association with EGFR in response to C. albicans or that mediated the interaction of other microbial pathogens with epithelial cells. Among these proteins, EGFR was found to associate with WW domain-binding protein 2, toll-interacting protein, interferon-induced transmembrane protein 3, and the globular C1q receptor (gC1qR) in viable epithelial cells. Each of these proteins was required for maximal endocytosis of C. albicans and they all regulated fungal-induced production of IL-1β and/or IL-8, either positively or negatively. gC1qR functioned as a key co-receptor with EGFR. Interacting with the C. albicans Als3 invasin, gC1qR was required for the fungus to stimulate both EGFR and the ephrin type-A receptor 2. The combination of gC1qR and EGFR was necessary for maximal endocytosis of C. albicans and secretion of IL-1β, IL-8, and GM-CSF. Thus, this work provides an atlas of proteins that associate with EGFR and identifies several that play a central role in the response of human oral epithelial cells to C. albicans infection.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.05.25.445718DOIDiscussion Paper
ORCID:
AuthorORCID
Lin, Jianfeng0000-0002-5202-6304
Swidergall, Marc0000-0002-5261-6267
Gaffen, Sarah L.0000-0001-8511-2041
Chou, Tsui-Fen0000-0003-2410-2186
Filler, Scott G.0000-0001-7278-3700
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. This version posted May 26, 2021. We thank Adam Diab for assistance with tissue culture. The work was support in part by NIH grants R01DE026600 and R01AI124566 to SGF, R00DE026856 to MS, and DE022550 to SLG. The QE Orbitrap used in these experiments was purchased with funds from the Department of Pediatrics at Harbor-UCLA Medical Center and the Henry L. Guenther Foundation.
Funders:
Funding AgencyGrant Number
NIHR01DE026600
NIHR01AI124566
NIHR00DE026856
NIHDE022550
Harbor-UCLA Medical CenterUNSPECIFIED
Henry L. Guenther FoundationUNSPECIFIED
Record Number:CaltechAUTHORS:20210528-084342141
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210528-084342141
Official Citation:The globular C1q receptor is required for epidermal growth factor receptor signaling during Candida albicans infection. Quynh T Phan, Jianfeng Lin, Norma V Solis, Michael Eng, Marc Swidergall, Feng Wang, Shan LI, Sarah L Gaffen, Tsui-Fen Chou, Scott G. Filler. bioRxiv 2021.05.25.445718; doi: https://doi.org/10.1101/2021.05.25.445718
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109293
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:28 May 2021 15:58
Last Modified:28 May 2021 15:58

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