Responses of reconstructed human epidermis to Trichophyton rubrum infection and impairment of infection by the inhibitor PD169316: Dermatophytosis inhibition by PD169316

Research output: Contribution to journalArticle

Abstract

Despite the threatening incidence of dermatophytosis, information is still lacking about the consequences of infection on epidermal barrier functions and about the keratinocyte responses that alert immune components. To identify the mechanisms involved, arthroconidia of the anthropophilic dermatophyte Trichophyton rubrum were prepared to infect reconstructed human epidermis (RHE) in vitro. Integrity of the barrier was monitored during infection by measurements of transepithelial electrical resistance and dye-permeation through the RHE. Expression and release of pro-inflammatory cytokines and antimicrobial peptides by keratinocytes inserted into the RHE were assessed, respectively, by quantitative reverse transcriptase–PCR (to analyze mRNA content in tissue extracts) and by ELISA (to detect proteins in culture media). Results reveal that infection by T. rubrum is responsible for disruption of the epidermal barrier, including loss of functional tight junctions. It additionally causes simultaneous expression and release of cytokines and antimicrobial peptides by keratinocytes. Potential involvement of the p38 mitogen-activated protein kinase signaling pathway was evaluated during infection by targeted inhibition of its activity. Intriguingly, among several p38 mitogen-activated protein kinase inhibitors, PD169316 alone was able to inhibit growth of T. rubrum on Sabouraud agar and to suppress the process of infection on RHE. This suggests that PD169316 acts on a specific target in dermatophytes themselves.

Original languageEnglish
Pages (from-to)2080-2089.e6
Number of pages50
JournalThe journal of investigative dermatology
Volume139
Issue number10
Early online date15 Apr 2019
DOIs
Publication statusPublished - 1 Oct 2019

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Tinea
Epidermis
p38 Mitogen-Activated Protein Kinases
Keratinocytes
Infection
Arthrodermataceae
Cytokines
Peptides
Acoustic impedance
Tissue Extracts
Protein Kinase Inhibitors
Permeation
Agar
Culture Media
Coloring Agents
Trichophyton
Tight Junctions
Messenger RNA
Electric Impedance
Enzyme-Linked Immunosorbent Assay

Cite this

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title = "Responses of reconstructed human epidermis to Trichophyton rubrum infection and impairment of infection by the inhibitor PD169316: Dermatophytosis inhibition by PD169316",
abstract = "Despite the threatening incidence of dermatophytosis, information is still lacking about the consequences of infection on epidermal barrier functions and about the keratinocyte responses that alert immune components. To identify the mechanisms involved, arthroconidia of the anthropophilic dermatophyte Trichophyton rubrum were prepared to infect reconstructed human epidermis (RHE) in vitro. Integrity of the barrier was monitored during infection by measurements of transepithelial electrical resistance and dye-permeation through the RHE. Expression and release of pro-inflammatory cytokines and antimicrobial peptides by keratinocytes inserted into the RHE were assessed, respectively, by quantitative reverse transcriptase–PCR (to analyze mRNA content in tissue extracts) and by ELISA (to detect proteins in culture media). Results reveal that infection by T. rubrum is responsible for disruption of the epidermal barrier, including loss of functional tight junctions. It additionally causes simultaneous expression and release of cytokines and antimicrobial peptides by keratinocytes. Potential involvement of the p38 mitogen-activated protein kinase signaling pathway was evaluated during infection by targeted inhibition of its activity. Intriguingly, among several p38 mitogen-activated protein kinase inhibitors, PD169316 alone was able to inhibit growth of T. rubrum on Sabouraud agar and to suppress the process of infection on RHE. This suggests that PD169316 acts on a specific target in dermatophytes themselves.",
author = "{\'E}milie Faway and Ludivine Cambier and {De Vuyst}, Evelyne and C{\'e}line Evrard and Marc Thiry and {Lambert De Rouvroit}, Catherine and Bernard Mignon and Yves Poumay",
year = "2019",
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T1 - Responses of reconstructed human epidermis to Trichophyton rubrum infection and impairment of infection by the inhibitor PD169316

T2 - Dermatophytosis inhibition by PD169316

AU - Faway, Émilie

AU - Cambier, Ludivine

AU - De Vuyst, Evelyne

AU - Evrard, Céline

AU - Thiry, Marc

AU - Lambert De Rouvroit, Catherine

AU - Mignon, Bernard

AU - Poumay, Yves

PY - 2019/10/1

Y1 - 2019/10/1

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AB - Despite the threatening incidence of dermatophytosis, information is still lacking about the consequences of infection on epidermal barrier functions and about the keratinocyte responses that alert immune components. To identify the mechanisms involved, arthroconidia of the anthropophilic dermatophyte Trichophyton rubrum were prepared to infect reconstructed human epidermis (RHE) in vitro. Integrity of the barrier was monitored during infection by measurements of transepithelial electrical resistance and dye-permeation through the RHE. Expression and release of pro-inflammatory cytokines and antimicrobial peptides by keratinocytes inserted into the RHE were assessed, respectively, by quantitative reverse transcriptase–PCR (to analyze mRNA content in tissue extracts) and by ELISA (to detect proteins in culture media). Results reveal that infection by T. rubrum is responsible for disruption of the epidermal barrier, including loss of functional tight junctions. It additionally causes simultaneous expression and release of cytokines and antimicrobial peptides by keratinocytes. Potential involvement of the p38 mitogen-activated protein kinase signaling pathway was evaluated during infection by targeted inhibition of its activity. Intriguingly, among several p38 mitogen-activated protein kinase inhibitors, PD169316 alone was able to inhibit growth of T. rubrum on Sabouraud agar and to suppress the process of infection on RHE. This suggests that PD169316 acts on a specific target in dermatophytes themselves.

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