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Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi
Prophylactic antifungal therapy is widely adopted clinically for critical patients and effective in reducing the morbidity of invasive fungal infection and improves outcomes of those diagnosed patients; however, it is not associated with higher overall survival. As intestinal commensal fungi play a...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545547/ https://www.ncbi.nlm.nih.gov/pubmed/34707775 http://dx.doi.org/10.1155/2021/2796700 |
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author | Sheng, Baifa Chen, Yihui Sun, Lihua Xu, Peng Han, Ben Li, Xiaolong Yin, Jiuheng Li, Teming Guan, Haidi Chen, Shuaishuai Wang, Qi Li, Chuangen Li, Shiqiang Jiang, Xianhong Wang, Peng He, Qiuyue Wang, Yong Xiao, Weidong Yang, Hua |
author_facet | Sheng, Baifa Chen, Yihui Sun, Lihua Xu, Peng Han, Ben Li, Xiaolong Yin, Jiuheng Li, Teming Guan, Haidi Chen, Shuaishuai Wang, Qi Li, Chuangen Li, Shiqiang Jiang, Xianhong Wang, Peng He, Qiuyue Wang, Yong Xiao, Weidong Yang, Hua |
author_sort | Sheng, Baifa |
collection | PubMed |
description | Prophylactic antifungal therapy is widely adopted clinically for critical patients and effective in reducing the morbidity of invasive fungal infection and improves outcomes of those diagnosed patients; however, it is not associated with higher overall survival. As intestinal commensal fungi play a fundamental role in the host immune response in health and disease, we propose that antifungal therapy may eliminate intestinal fungi and aggravate another critical syndrome, sepsis. Here, with murine sepsis model, we found that antifungal therapy with fluconazole dismissed intestinal fungal burden and aggravated endotoxin-induced but no gram-positive bacteria-induced sepsis. Nevertheless, antifungal therapy did not exert its detrimental effect on germ-free mice. Moreover, colonizing more commensal fungi in the mouse intestine or administration of fungal cell wall component mannan protected the mice from endotoxin-induced sepsis. On the molecular level, we demonstrated that antifungal therapy aggravated endotoxin sepsis through promoting Gasdermin D cleavage in the distal small intestine. Intestinal colonization with commensal fungi inhibited Gasdermin D cleavage in response to lipopolysaccharide challenge. These findings show that intestinal fungi inhibit Gasdermin D-mediated pyroptosis and protect the mice from endotoxin-induced sepsis. This study demonstrates the protective role of intestinal fungi in the pathogenesis of endotoxin-induced sepsis in the laboratory. It will undoubtedly prompt us to study the relationship between antifungal therapy and sepsis in critical patients who are susceptible to endotoxin-induced sepsis in the future. |
format | Online Article Text |
id | pubmed-8545547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-85455472021-10-26 Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi Sheng, Baifa Chen, Yihui Sun, Lihua Xu, Peng Han, Ben Li, Xiaolong Yin, Jiuheng Li, Teming Guan, Haidi Chen, Shuaishuai Wang, Qi Li, Chuangen Li, Shiqiang Jiang, Xianhong Wang, Peng He, Qiuyue Wang, Yong Xiao, Weidong Yang, Hua Oxid Med Cell Longev Research Article Prophylactic antifungal therapy is widely adopted clinically for critical patients and effective in reducing the morbidity of invasive fungal infection and improves outcomes of those diagnosed patients; however, it is not associated with higher overall survival. As intestinal commensal fungi play a fundamental role in the host immune response in health and disease, we propose that antifungal therapy may eliminate intestinal fungi and aggravate another critical syndrome, sepsis. Here, with murine sepsis model, we found that antifungal therapy with fluconazole dismissed intestinal fungal burden and aggravated endotoxin-induced but no gram-positive bacteria-induced sepsis. Nevertheless, antifungal therapy did not exert its detrimental effect on germ-free mice. Moreover, colonizing more commensal fungi in the mouse intestine or administration of fungal cell wall component mannan protected the mice from endotoxin-induced sepsis. On the molecular level, we demonstrated that antifungal therapy aggravated endotoxin sepsis through promoting Gasdermin D cleavage in the distal small intestine. Intestinal colonization with commensal fungi inhibited Gasdermin D cleavage in response to lipopolysaccharide challenge. These findings show that intestinal fungi inhibit Gasdermin D-mediated pyroptosis and protect the mice from endotoxin-induced sepsis. This study demonstrates the protective role of intestinal fungi in the pathogenesis of endotoxin-induced sepsis in the laboratory. It will undoubtedly prompt us to study the relationship between antifungal therapy and sepsis in critical patients who are susceptible to endotoxin-induced sepsis in the future. Hindawi 2021-10-18 /pmc/articles/PMC8545547/ /pubmed/34707775 http://dx.doi.org/10.1155/2021/2796700 Text en Copyright © 2021 Baifa Sheng et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Sheng, Baifa Chen, Yihui Sun, Lihua Xu, Peng Han, Ben Li, Xiaolong Yin, Jiuheng Li, Teming Guan, Haidi Chen, Shuaishuai Wang, Qi Li, Chuangen Li, Shiqiang Jiang, Xianhong Wang, Peng He, Qiuyue Wang, Yong Xiao, Weidong Yang, Hua Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi |
title | Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi |
title_full | Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi |
title_fullStr | Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi |
title_full_unstemmed | Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi |
title_short | Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi |
title_sort | antifungal treatment aggravates sepsis through the elimination of intestinal fungi |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545547/ https://www.ncbi.nlm.nih.gov/pubmed/34707775 http://dx.doi.org/10.1155/2021/2796700 |
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