Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivo
Abstract Burkholderia cenocepacia (B. cenocepacia) is an opportunistic bacterium; causing severe life threatening systemic infections in immunocompromised individuals including cystic fibrosis patients. The lack of gasdermin D (GSDMD) protects mice against endotoxin lipopolysaccharide (LPS) shock. O...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-79201-5 |
| _version_ | 1818431632122576896 |
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| author | Shady Estfanous Kathrin Krause Midhun N. K. Anne Mostafa Eltobgy Kyle Caution Arwa Abu Khweek Kaitlin Hamilton Asmaa Badr Kylene Daily Cierra Carafice Daniel Baetzhold Xiaoli Zhang Tianliang Li Haitao Wen Mikhail A. Gavrilin Hesham Haffez Sameh Soror Amal O. Amer |
| author_facet | Shady Estfanous Kathrin Krause Midhun N. K. Anne Mostafa Eltobgy Kyle Caution Arwa Abu Khweek Kaitlin Hamilton Asmaa Badr Kylene Daily Cierra Carafice Daniel Baetzhold Xiaoli Zhang Tianliang Li Haitao Wen Mikhail A. Gavrilin Hesham Haffez Sameh Soror Amal O. Amer |
| author_sort | Shady Estfanous |
| collection | DOAJ |
| description | Abstract Burkholderia cenocepacia (B. cenocepacia) is an opportunistic bacterium; causing severe life threatening systemic infections in immunocompromised individuals including cystic fibrosis patients. The lack of gasdermin D (GSDMD) protects mice against endotoxin lipopolysaccharide (LPS) shock. On the other hand, GSDMD promotes mice survival in response to certain bacterial infections. However, the role of GSDMD during B. cenocepacia infection is not yet determined. Our in vitro study shows that GSDMD restricts B. cenocepacia replication within macrophages independent of its role in cell death through promoting mitochondrial reactive oxygen species (mROS) production. mROS is known to stimulate autophagy, hence, the inhibition of mROS or the absence of GSDMD during B. cenocepacia infections reduces autophagy which plays a critical role in the restriction of the pathogen. GSDMD promotes inflammation in response to B. cenocepacia through mediating the release of inflammasome dependent cytokine (IL-1β) and an independent one (CXCL1) (KC). Additionally, different B. cenocepacia secretory systems (T3SS, T4SS, and T6SS) contribute to inflammasome activation together with bacterial survival within macrophages. In vivo study confirmed the in vitro findings and showed that GSDMD restricts B. cenocepacia infection and dissemination and stimulates autophagy in response to B. cenocepacia. Nevertheless, GSDMD promotes lung inflammation and necrosis in response to B. cenocepacia without altering mice survival. This study describes the double-edged functions of GSDMD in response to B. cenocepacia infection and shows the importance of GSDMD-mediated mROS in restriction of B. cenocepacia. |
| first_indexed | 2024-12-14T15:52:23Z |
| format | Article |
| id | doaj.art-dfc42d70a6394957ad2316ed4514e290 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:52:23Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dfc42d70a6394957ad2316ed4514e2902022-12-21T22:55:21ZengNature PortfolioScientific Reports2045-23222021-01-0111112010.1038/s41598-020-79201-5Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivoShady Estfanous0Kathrin Krause1Midhun N. K. Anne2Mostafa Eltobgy3Kyle Caution4Arwa Abu Khweek5Kaitlin Hamilton6Asmaa Badr7Kylene Daily8Cierra Carafice9Daniel Baetzhold10Xiaoli Zhang11Tianliang Li12Haitao Wen13Mikhail A. Gavrilin14Hesham Haffez15Sameh Soror16Amal O. Amer17Department of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityCenter for Biostatistics, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityDepartment of Internal Medicine, Ohio State UniversityBiochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan UniversityBiochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan UniversityDepartment of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State UniversityAbstract Burkholderia cenocepacia (B. cenocepacia) is an opportunistic bacterium; causing severe life threatening systemic infections in immunocompromised individuals including cystic fibrosis patients. The lack of gasdermin D (GSDMD) protects mice against endotoxin lipopolysaccharide (LPS) shock. On the other hand, GSDMD promotes mice survival in response to certain bacterial infections. However, the role of GSDMD during B. cenocepacia infection is not yet determined. Our in vitro study shows that GSDMD restricts B. cenocepacia replication within macrophages independent of its role in cell death through promoting mitochondrial reactive oxygen species (mROS) production. mROS is known to stimulate autophagy, hence, the inhibition of mROS or the absence of GSDMD during B. cenocepacia infections reduces autophagy which plays a critical role in the restriction of the pathogen. GSDMD promotes inflammation in response to B. cenocepacia through mediating the release of inflammasome dependent cytokine (IL-1β) and an independent one (CXCL1) (KC). Additionally, different B. cenocepacia secretory systems (T3SS, T4SS, and T6SS) contribute to inflammasome activation together with bacterial survival within macrophages. In vivo study confirmed the in vitro findings and showed that GSDMD restricts B. cenocepacia infection and dissemination and stimulates autophagy in response to B. cenocepacia. Nevertheless, GSDMD promotes lung inflammation and necrosis in response to B. cenocepacia without altering mice survival. This study describes the double-edged functions of GSDMD in response to B. cenocepacia infection and shows the importance of GSDMD-mediated mROS in restriction of B. cenocepacia.https://doi.org/10.1038/s41598-020-79201-5 |
| spellingShingle | Shady Estfanous Kathrin Krause Midhun N. K. Anne Mostafa Eltobgy Kyle Caution Arwa Abu Khweek Kaitlin Hamilton Asmaa Badr Kylene Daily Cierra Carafice Daniel Baetzhold Xiaoli Zhang Tianliang Li Haitao Wen Mikhail A. Gavrilin Hesham Haffez Sameh Soror Amal O. Amer Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivo Scientific Reports |
| title | Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivo |
| title_full | Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivo |
| title_fullStr | Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivo |
| title_full_unstemmed | Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivo |
| title_short | Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivo |
| title_sort | gasdermin d restricts burkholderia cenocepacia infection in vitro and in vivo |
| url | https://doi.org/10.1038/s41598-020-79201-5 |
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