Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
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
_version_ 1784590020449927168
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
work_keys_str_mv AT shengbaifa antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT chenyihui antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT sunlihua antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT xupeng antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT hanben antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT lixiaolong antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT yinjiuheng antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT liteming antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT guanhaidi antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT chenshuaishuai antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT wangqi antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT lichuangen antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT lishiqiang antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT jiangxianhong antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT wangpeng antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT heqiuyue antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT wangyong antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT xiaoweidong antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi
AT yanghua antifungaltreatmentaggravatessepsisthroughtheeliminationofintestinalfungi