Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants
Abstract Burn wounds are highly susceptible sites for colonization and infection by bacteria and fungi. Large wound surface, impaired local immunity, and broad-spectrum antibiotic therapy support growth of opportunistic fungi such as Candida albicans, which may lead to invasive candidiasis. Currentl...
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2020
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oai:doaj.org-article:ba837634657b4b858d2cc5178fea1d412021-12-02T16:18:04ZActive neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants10.1038/s41598-020-78387-y2045-2322https://doaj.org/article/ba837634657b4b858d2cc5178fea1d412020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78387-yhttps://doaj.org/toc/2045-2322Abstract Burn wounds are highly susceptible sites for colonization and infection by bacteria and fungi. Large wound surface, impaired local immunity, and broad-spectrum antibiotic therapy support growth of opportunistic fungi such as Candida albicans, which may lead to invasive candidiasis. Currently, it remains unknown whether depressed host defenses or fungal virulence drive the progression of burn wound candidiasis. Here we established an ex vivo burn wound model, where wounds were inflicted by applying preheated soldering iron to human skin explants, resulting in highly reproducible deep second-degree burn wounds. Eschar removal by debridement allowed for deeper C. albicans penetration into the burned tissue associated with prominent filamentation. Active migration of resident tissue neutrophils towards the damaged tissue and release of pro-inflammatory cytokine IL-1β accompanied the burn. The neutrophil recruitment was further increased upon supplementation of the model with fresh immune cells. Wound area and depth decreased over time, indicating healing of the damaged tissue. Importantly, prominent neutrophil presence at the infected site correlated to the limited penetration of C. albicans into the burned tissue. Altogether, we established a reproducible burn wound model of candidiasis using ex vivo human skin explants, where immune responses actively control the progression of infection and promote tissue healing.Christin von MüllerFionnuala BulmanLysett WagnerDaniel RosenbergerAlessandra MaroldaOliver KurzaiPetra EißmannIlse D. JacobsenBirgit PernerPeter HemmerichSlavena VylkovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) |
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Medicine R Science Q Christin von Müller Fionnuala Bulman Lysett Wagner Daniel Rosenberger Alessandra Marolda Oliver Kurzai Petra Eißmann Ilse D. Jacobsen Birgit Perner Peter Hemmerich Slavena Vylkova Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants |
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Abstract Burn wounds are highly susceptible sites for colonization and infection by bacteria and fungi. Large wound surface, impaired local immunity, and broad-spectrum antibiotic therapy support growth of opportunistic fungi such as Candida albicans, which may lead to invasive candidiasis. Currently, it remains unknown whether depressed host defenses or fungal virulence drive the progression of burn wound candidiasis. Here we established an ex vivo burn wound model, where wounds were inflicted by applying preheated soldering iron to human skin explants, resulting in highly reproducible deep second-degree burn wounds. Eschar removal by debridement allowed for deeper C. albicans penetration into the burned tissue associated with prominent filamentation. Active migration of resident tissue neutrophils towards the damaged tissue and release of pro-inflammatory cytokine IL-1β accompanied the burn. The neutrophil recruitment was further increased upon supplementation of the model with fresh immune cells. Wound area and depth decreased over time, indicating healing of the damaged tissue. Importantly, prominent neutrophil presence at the infected site correlated to the limited penetration of C. albicans into the burned tissue. Altogether, we established a reproducible burn wound model of candidiasis using ex vivo human skin explants, where immune responses actively control the progression of infection and promote tissue healing. |
format |
article |
author |
Christin von Müller Fionnuala Bulman Lysett Wagner Daniel Rosenberger Alessandra Marolda Oliver Kurzai Petra Eißmann Ilse D. Jacobsen Birgit Perner Peter Hemmerich Slavena Vylkova |
author_facet |
Christin von Müller Fionnuala Bulman Lysett Wagner Daniel Rosenberger Alessandra Marolda Oliver Kurzai Petra Eißmann Ilse D. Jacobsen Birgit Perner Peter Hemmerich Slavena Vylkova |
author_sort |
Christin von Müller |
title |
Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants |
title_short |
Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants |
title_full |
Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants |
title_fullStr |
Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants |
title_full_unstemmed |
Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants |
title_sort |
active neutrophil responses counteract candida albicans burn wound infection of ex vivo human skin explants |
publisher |
Nature Portfolio |
publishDate |
2020 |
url |
https://doaj.org/article/ba837634657b4b858d2cc5178fea1d41 |
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