RETRACTED: The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model
ABSTRACT Pertussis, also known as whooping cough, is a contagious respiratory disease caused by the Gram-negative bacterium Bordetella pertussis. This disease is characterized by severe and uncontrollable coughing, which imposes a significant burden on patients. However, its etiological agent and th...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-04-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03197-21 |
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| author | Yukihiro Hiramatsu Koichiro Suzuki Takashi Nishida Naoki Onoda Takashi Satoh Shizuo Akira Masahito Ikawa Hiroko Ikeda Junzo Kamei Sandra Derouiche Makoto Tominaga Yasuhiko Horiguchi |
| author_facet | Yukihiro Hiramatsu Koichiro Suzuki Takashi Nishida Naoki Onoda Takashi Satoh Shizuo Akira Masahito Ikawa Hiroko Ikeda Junzo Kamei Sandra Derouiche Makoto Tominaga Yasuhiko Horiguchi |
| author_sort | Yukihiro Hiramatsu |
| collection | DOAJ |
| description | ABSTRACT Pertussis, also known as whooping cough, is a contagious respiratory disease caused by the Gram-negative bacterium Bordetella pertussis. This disease is characterized by severe and uncontrollable coughing, which imposes a significant burden on patients. However, its etiological agent and the mechanism are totally unknown because of a lack of versatile animal models that reproduce the cough. Here, we present a mouse model that reproduces coughing after intranasal inoculation with the bacterium or its components and demonstrate that lipooligosaccharide (LOS), pertussis toxin (PTx), and Vag8 of the bacterium cooperatively function to cause coughing. Bradykinin induced by LOS sensitized a transient receptor potential ion channel, TRPV1, which acts as a sensor to evoke the cough reflex. Vag8 further increased bradykinin levels by inhibiting the C1 esterase inhibitor, the major downregulator of the contact system, which generates bradykinin. PTx inhibits intrinsic negative regulation systems for TRPV1 through the inactivation of Gi GTPases. Our findings provide a basis to answer long-standing questions on the pathophysiology of pertussis cough. IMPORTANCE The Gram-negative bacterium Bordetella pertussis causes a respiratory disease called whooping cough, or pertussis. This disease is characterized by paroxysmal coughing, the mechanism of which has not been intensively studied because of a lack of versatile animal models that reproduce the cough. In this study, we present a mouse model that reproduces coughing after intranasal inoculation with the bacterium or its components. Using this model, we demonstrate that lipooligosaccharide, Vag8, and pertussis toxin of the bacteria cooperatively function to cause coughing. Our results also indicate that bradykinin, an inflammatory mediator, and TRPV1, an ion channel linked to nociceptive signaling, are host factors involved in the coughing mechanism. |
| format | Article |
| id | doaj-art-8e702cc8a23d48fe9f49e88afccab788 |
| institution | Kabale University |
| issn | 2150-7511 |
| language | English |
| publishDate | 2022-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj-art-8e702cc8a23d48fe9f49e88afccab7882025-02-05T14:15:03ZengAmerican Society for MicrobiologymBio2150-75112022-04-0113210.1128/mbio.03197-21RETRACTED: The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing ModelYukihiro Hiramatsu0Koichiro Suzuki1Takashi Nishida2Naoki Onoda3Takashi Satoh4Shizuo Akira5Masahito Ikawa6Hiroko Ikeda7Junzo Kamei8Sandra Derouiche9Makoto Tominaga10Yasuhiko Horiguchi11Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanLaboratory of Host Defense, World Premier Institute Immunology Frontier Research Center, Osaka University, Suita, Osaka, JapanLaboratory of Host Defense, World Premier Institute Immunology Frontier Research Center, Osaka University, Suita, Osaka, JapanDepartment of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, JapanJuntendo Advanced Research Institute for Health Science, Juntendo University, Tokyo, JapanDivision of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Aichi, JapanDivision of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Aichi, JapanDepartment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanABSTRACT Pertussis, also known as whooping cough, is a contagious respiratory disease caused by the Gram-negative bacterium Bordetella pertussis. This disease is characterized by severe and uncontrollable coughing, which imposes a significant burden on patients. However, its etiological agent and the mechanism are totally unknown because of a lack of versatile animal models that reproduce the cough. Here, we present a mouse model that reproduces coughing after intranasal inoculation with the bacterium or its components and demonstrate that lipooligosaccharide (LOS), pertussis toxin (PTx), and Vag8 of the bacterium cooperatively function to cause coughing. Bradykinin induced by LOS sensitized a transient receptor potential ion channel, TRPV1, which acts as a sensor to evoke the cough reflex. Vag8 further increased bradykinin levels by inhibiting the C1 esterase inhibitor, the major downregulator of the contact system, which generates bradykinin. PTx inhibits intrinsic negative regulation systems for TRPV1 through the inactivation of Gi GTPases. Our findings provide a basis to answer long-standing questions on the pathophysiology of pertussis cough. IMPORTANCE The Gram-negative bacterium Bordetella pertussis causes a respiratory disease called whooping cough, or pertussis. This disease is characterized by paroxysmal coughing, the mechanism of which has not been intensively studied because of a lack of versatile animal models that reproduce the cough. In this study, we present a mouse model that reproduces coughing after intranasal inoculation with the bacterium or its components. Using this model, we demonstrate that lipooligosaccharide, Vag8, and pertussis toxin of the bacteria cooperatively function to cause coughing. Our results also indicate that bradykinin, an inflammatory mediator, and TRPV1, an ion channel linked to nociceptive signaling, are host factors involved in the coughing mechanism.https://journals.asm.org/doi/10.1128/mbio.03197-21Bordetella pertussisbradykininTRPV1Vag8coughpertussis toxin |
| spellingShingle | Yukihiro Hiramatsu Koichiro Suzuki Takashi Nishida Naoki Onoda Takashi Satoh Shizuo Akira Masahito Ikawa Hiroko Ikeda Junzo Kamei Sandra Derouiche Makoto Tominaga Yasuhiko Horiguchi RETRACTED: The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model mBio Bordetella pertussis bradykinin TRPV1 Vag8 cough pertussis toxin |
| title | RETRACTED: The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model |
| title_full | RETRACTED: The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model |
| title_fullStr | RETRACTED: The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model |
| title_full_unstemmed | RETRACTED: The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model |
| title_short | RETRACTED: The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model |
| title_sort | retracted the mechanism of pertussis cough revealed by the mouse coughing model |
| topic | Bordetella pertussis bradykinin TRPV1 Vag8 cough pertussis toxin |
| url | https://journals.asm.org/doi/10.1128/mbio.03197-21 |
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