Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice
BackgroundAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1137369/full |
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| author | Xiao Wu Run-Feng Li Run-Feng Li Zheng-Shi Lin Chuang Xiao Bin Liu Kai-Lin Mai Hong-Xia Zhou De-You Zeng Sha Cheng Yun-Ceng Weng Jin Zhao Rui-Feng Chen Hai-Ming Jiang Li-Ping Chen Ling-Zhu Deng Pei-Fang Xie Wei-Min Yang Xue-Shan Xia Zi-Feng Yang Zi-Feng Yang Zi-Feng Yang Zi-Feng Yang |
| author_facet | Xiao Wu Run-Feng Li Run-Feng Li Zheng-Shi Lin Chuang Xiao Bin Liu Kai-Lin Mai Hong-Xia Zhou De-You Zeng Sha Cheng Yun-Ceng Weng Jin Zhao Rui-Feng Chen Hai-Ming Jiang Li-Ping Chen Ling-Zhu Deng Pei-Fang Xie Wei-Min Yang Xue-Shan Xia Zi-Feng Yang Zi-Feng Yang Zi-Feng Yang Zi-Feng Yang |
| author_sort | Xiao Wu |
| collection | DOAJ |
| description | BackgroundAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not entirely understood.MethodsWe developed a mouse model of AECOPD by cigarette smoke exposure and sequential infection with influenza H1N1 virus and non-typeable Haemophilus influenzae (NTHi). Viral and bacterial titer was determined using MDCK cells and chocolate agar plates, respectively. The levels of cytokines, adhesion molecules, and inflammatory cells in the lungs were measured using Bio-Plex and flow cytometry assays. Gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between cytokines and gut microbiota were determined using Spearman’s rank correlation coefficient test.ResultsCoinfection with H1N1 and NTHi resulted in more severe lung injury, higher mortality, declined lung function in COPD mice. H1N1 enhanced NTHi growth in the lungs, but NTHi had no effect on H1N1. In addition, coinfection increased the levels of cytokines and adhesion molecules, as well as immune cells including total and M1 macrophages, neutrophils, monocytes, NK cells, and CD4 + T cells. In contrast, alveolar macrophages were depleted. Furthermore, coinfection caused a decline in the diversity of gut bacteria. Muribaculaceae, Lactobacillus, Akkermansia, Lachnospiraceae, and Rikenella were further found to be negatively correlated with cytokine levels, whereas Bacteroides was positively correlated.ConclusionCoinfection with H1N1 and NTHi causes a deterioration in COPD mice due to increased lung inflammation, which is correlated with dysbiosis of the gut microbiota. |
| first_indexed | 2024-04-09T20:36:36Z |
| format | Article |
| id | doaj.art-44f9888ea79b4637b9911237c0447dbb |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-09T20:36:36Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-44f9888ea79b4637b9911237c0447dbb2023-03-30T07:44:25ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-03-011410.3389/fmicb.2023.11373691137369Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD miceXiao Wu0Run-Feng Li1Run-Feng Li2Zheng-Shi Lin3Chuang Xiao4Bin Liu5Kai-Lin Mai6Hong-Xia Zhou7De-You Zeng8Sha Cheng9Yun-Ceng Weng10Jin Zhao11Rui-Feng Chen12Hai-Ming Jiang13Li-Ping Chen14Ling-Zhu Deng15Pei-Fang Xie16Wei-Min Yang17Xue-Shan Xia18Zi-Feng Yang19Zi-Feng Yang20Zi-Feng Yang21Zi-Feng Yang22State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangzhou Laboratory, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaSchool of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDongguan People’s Hospital, Dongguan, ChinaSchool of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaThe Affiliated Anning First Hospital and Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, ChinaSchool of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaThe Affiliated Anning First Hospital and Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangzhou Laboratory, Guangzhou, ChinaGuangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, Guangzhou, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, ChinaBackgroundAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not entirely understood.MethodsWe developed a mouse model of AECOPD by cigarette smoke exposure and sequential infection with influenza H1N1 virus and non-typeable Haemophilus influenzae (NTHi). Viral and bacterial titer was determined using MDCK cells and chocolate agar plates, respectively. The levels of cytokines, adhesion molecules, and inflammatory cells in the lungs were measured using Bio-Plex and flow cytometry assays. Gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between cytokines and gut microbiota were determined using Spearman’s rank correlation coefficient test.ResultsCoinfection with H1N1 and NTHi resulted in more severe lung injury, higher mortality, declined lung function in COPD mice. H1N1 enhanced NTHi growth in the lungs, but NTHi had no effect on H1N1. In addition, coinfection increased the levels of cytokines and adhesion molecules, as well as immune cells including total and M1 macrophages, neutrophils, monocytes, NK cells, and CD4 + T cells. In contrast, alveolar macrophages were depleted. Furthermore, coinfection caused a decline in the diversity of gut bacteria. Muribaculaceae, Lactobacillus, Akkermansia, Lachnospiraceae, and Rikenella were further found to be negatively correlated with cytokine levels, whereas Bacteroides was positively correlated.ConclusionCoinfection with H1N1 and NTHi causes a deterioration in COPD mice due to increased lung inflammation, which is correlated with dysbiosis of the gut microbiota.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1137369/fullCOPDinfluenzainfluenzaemiceinflammationmicrobiota |
| spellingShingle | Xiao Wu Run-Feng Li Run-Feng Li Zheng-Shi Lin Chuang Xiao Bin Liu Kai-Lin Mai Hong-Xia Zhou De-You Zeng Sha Cheng Yun-Ceng Weng Jin Zhao Rui-Feng Chen Hai-Ming Jiang Li-Ping Chen Ling-Zhu Deng Pei-Fang Xie Wei-Min Yang Xue-Shan Xia Zi-Feng Yang Zi-Feng Yang Zi-Feng Yang Zi-Feng Yang Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice Frontiers in Microbiology COPD influenza influenzae mice inflammation microbiota |
| title | Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice |
| title_full | Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice |
| title_fullStr | Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice |
| title_full_unstemmed | Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice |
| title_short | Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice |
| title_sort | coinfection with influenza virus and non typeable haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in copd mice |
| topic | COPD influenza influenzae mice inflammation microbiota |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1137369/full |
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