IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis

Heather R. Conti; Vincent M. Bruno; Erin E. Childs; Sean Daugherty; Joseph P. Hunter; Bemnet G. Mengesha; Danielle L. Saevig; Matthew R. Hendricks; Bianca M. Coleman; Lucas Brane; Norma Solis; J. Agustin Cruz; Akash H. Verma; Abhishek V. Garg; Amy G. Hise; Jonathan P. Richardson; Julian R. Naglik; Scott G. Filler; Jay K. Kolls; Satrajit Sinha; Sarah L. Gaffen

doi:10.1016/j.chom.2016.10.001

IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis

Heather R. Conti
, Vincent M. Bruno
, Erin E. Childs
, Sean Daugherty
, Joseph P. Hunter
, Bemnet G. Mengesha
, Danielle L. Saevig
, Matthew R. Hendricks
, Bianca M. Coleman
, Lucas Brane
, Norma Solis
, J. Agustin Cruz
, Akash H. Verma
, Abhishek V. Garg
, Amy G. Hise
, Jonathan P. Richardson
, Julian R. Naglik
, Scott G. Filler
, Jay K. Kolls
, Satrajit Sinha

Sarah L. Gaffen

Biochemistry

University at Buffalo

University of Pittsburgh
University of Toledo
University of Maryland, Baltimore
University of California at Los Angeles
Case Western Reserve University
Louis Stokes Cleveland VA Medical Center
King's College London

Research output: Contribution to journal › Article › peer-review

162 Scopus citations

Abstract

Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras, we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17ra^ΔK13). Following oral Candida infection, Il17ra^ΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra^−/− mice. Susceptibility in Il17ra^ΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3^−/− mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3 expression.

Original language	English
Pages (from-to)	606-617
Number of pages	12
Journal	Cell Host and Microbe
Volume	20
Issue number	5
DOIs	https://doi.org/10.1016/j.chom.2016.10.001
State	Published - Nov 9 2016

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Conti, H. R., Bruno, V. M., Childs, E. E., Daugherty, S., Hunter, J. P., Mengesha, B. G., Saevig, D. L., Hendricks, M. R., Coleman, B. M., Brane, L., Solis, N., Cruz, J. A., Verma, A. H., Garg, A. V., Hise, A. G., Richardson, J. P., Naglik, J. R., Filler, S. G., Kolls, J. K., ... Gaffen, S. L. (2016). IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis. Cell Host and Microbe, 20(5), 606-617. https://doi.org/10.1016/j.chom.2016.10.001

@article{3110eeb404f24263a68acd0954ce99da,

title = "IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis",

abstract = "Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras, we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17raΔK13). Following oral Candida infection, Il17raΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra−/− mice. Susceptibility in Il17raΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3−/− mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3 expression.",

author = "Conti, \{Heather R.\} and Bruno, \{Vincent M.\} and Childs, \{Erin E.\} and Sean Daugherty and Hunter, \{Joseph P.\} and Mengesha, \{Bemnet G.\} and Saevig, \{Danielle L.\} and Hendricks, \{Matthew R.\} and Coleman, \{Bianca M.\} and Lucas Brane and Norma Solis and Cruz, \{J. Agustin\} and Verma, \{Akash H.\} and Garg, \{Abhishek V.\} and Hise, \{Amy G.\} and Richardson, \{Jonathan P.\} and Naglik, \{Julian R.\} and Filler, \{Scott G.\} and Kolls, \{Jay K.\} and Satrajit Sinha and Gaffen, \{Sarah L.\}",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = nov,

day = "9",

doi = "10.1016/j.chom.2016.10.001",

language = "English",

volume = "20",

pages = "606--617",

journal = "Cell Host and Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "5",

}

Conti, HR, Bruno, VM, Childs, EE, Daugherty, S, Hunter, JP, Mengesha, BG, Saevig, DL, Hendricks, MR, Coleman, BM, Brane, L, Solis, N, Cruz, JA, Verma, AH, Garg, AV, Hise, AG, Richardson, JP, Naglik, JR, Filler, SG, Kolls, JK, Sinha, S & Gaffen, SL 2016, 'IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis', Cell Host and Microbe, vol. 20, no. 5, pp. 606-617. https://doi.org/10.1016/j.chom.2016.10.001

TY - JOUR

T1 - IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis

AU - Conti, Heather R.

AU - Bruno, Vincent M.

AU - Childs, Erin E.

AU - Daugherty, Sean

AU - Hunter, Joseph P.

AU - Mengesha, Bemnet G.

AU - Saevig, Danielle L.

AU - Hendricks, Matthew R.

AU - Coleman, Bianca M.

AU - Brane, Lucas

AU - Solis, Norma

AU - Cruz, J. Agustin

AU - Verma, Akash H.

AU - Garg, Abhishek V.

AU - Hise, Amy G.

AU - Richardson, Jonathan P.

AU - Naglik, Julian R.

AU - Filler, Scott G.

AU - Kolls, Jay K.

AU - Sinha, Satrajit

AU - Gaffen, Sarah L.

PY - 2016/11/9

Y1 - 2016/11/9

N2 - Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras, we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17raΔK13). Following oral Candida infection, Il17raΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra−/− mice. Susceptibility in Il17raΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3−/− mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3 expression.

AB - Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras, we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17raΔK13). Following oral Candida infection, Il17raΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra−/− mice. Susceptibility in Il17raΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3−/− mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3 expression.

UR - https://www.scopus.com/pages/publications/84994719165

U2 - 10.1016/j.chom.2016.10.001

DO - 10.1016/j.chom.2016.10.001

M3 - Article

C2 - 27923704

SN - 1931-3128

VL - 20

SP - 606

EP - 617

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 5

ER -

IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis

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