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 SinhaSarah L. Gaffen

Centre for Host Microbiome Interactions

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Abstract

Summary 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.

Original language	English
Pages (from-to)	606–617
Journal	Cell Host & Microbe
Volume	20
Issue number	5
Early online date	27 Oct 2016
DOIs	https://doi.org/10.1016/j.chom.2016.10.001
Publication status	Published - 9 Nov 2016

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IL-17 Receptor Signaling_CONTI_Accepted21September2016_GREEN AAMAccepted author manuscript, 2.08 MBLicence: CC BY-NC-ND

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Conti, HR., Bruno, VM., Childs, EE., Daugherty, S., Hunter, JP., Mengesha, BG., Saevig, DL., Hendricks, MR., Coleman, BM., Brane, L., Solis, N., Cruz, J. A., Verma, AH., Garg, AV., Hise, AG., Richardson, J. P., Naglik, J. R., Filler, SG., Kolls, JK., ... Gaffen, SL. (2016). IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis. Cell Host & Microbe, 20(5), 606–617. https://doi.org/10.1016/j.chom.2016.10.001

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

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

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

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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 & 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 - Summary 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 - Summary 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.

U2 - 10.1016/j.chom.2016.10.001

DO - 10.1016/j.chom.2016.10.001

M3 - Article

SN - 1931-3128

VL - 20

SP - 606

EP - 617

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 5

ER -

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

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