Host immune response mediates changes in cagA copy number and virulence potential of Helicobacter pylori
Helicobacter pylori is the major risk factor for gastric cancer. H. pylori harboring the type IV secretion system (T4SS) and its effector CagA encoded on the cag pathogenicity Island (cagPAI) increases the risk. H. pylori PMSS1 has a multi-cagA genotype, modulating cagA copy number dynamically from...
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| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2044721 |
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| author | Sungil Jang Lori M. Hansen Hanfu Su Jay V. Solnick Jeong-Heon Cha |
| author_facet | Sungil Jang Lori M. Hansen Hanfu Su Jay V. Solnick Jeong-Heon Cha |
| author_sort | Sungil Jang |
| collection | DOAJ |
| description | Helicobacter pylori is the major risk factor for gastric cancer. H. pylori harboring the type IV secretion system (T4SS) and its effector CagA encoded on the cag pathogenicity Island (cagPAI) increases the risk. H. pylori PMSS1 has a multi-cagA genotype, modulating cagA copy number dynamically from zero to four copies. To examine the effect of the immune response on cagA copy number change, we utilized a mouse model with different immune status. PMSS1 recovered from Rag1−/− mice, lacking functional T or B cells, retained more cagA copies. PMSS1 recovered from Il10−/− mice, showing intense inflammation, had fewer cagA copies compared to those recovered from wild-type mice. Moreover, cagA copy number of PMSS1 recovered from wild-type and Il10−/− mice was positively correlated with the capacity to induce IL-8 secretion at four weeks of infection. Since recombination in cagY influences T4SS function, including CagA translocation and IL-8 induction, we constructed a multiple linear regression model to predict H. pylori-induced IL-8 expression based on cagA copy number and cagY recombination status; H. pylori induces more IL-8 secretion when the strain has more cagA copies and intact cagY. This study shows that H. pylori PMSS1 in mice with less intense immune response possess higher cagA copy number than those infected in mice with more intense immune response and thus the multi-cagA genotype, along with cagY recombination, functions as an immune-sensitive regulator of H. pylori virulence. |
| format | Article |
| id | doaj-art-59a8fdca625a4a7caee076507d95bfd8 |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-59a8fdca625a4a7caee076507d95bfd82025-08-20T02:29:56ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2044721Host immune response mediates changes in cagA copy number and virulence potential of Helicobacter pyloriSungil Jang0Lori M. Hansen1Hanfu Su2Jay V. Solnick3Jeong-Heon Cha4Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, The Graduate School, BK21 Four Project, Yonsei University College of Dentistry, Seoul, Republic of KoreaCenter for Immunology and Infectious Diseases; Departments of Medicine and of Microbiology and Immunology, School of Medicine; University of California Davis, Davis, CA, USAAffiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, ChinaCenter for Immunology and Infectious Diseases; Departments of Medicine and of Microbiology and Immunology, School of Medicine; University of California Davis, Davis, CA, USADepartment of Oral Biology, Oral Science Research Center, Department of Applied Life Science, The Graduate School, BK21 Four Project, Yonsei University College of Dentistry, Seoul, Republic of KoreaHelicobacter pylori is the major risk factor for gastric cancer. H. pylori harboring the type IV secretion system (T4SS) and its effector CagA encoded on the cag pathogenicity Island (cagPAI) increases the risk. H. pylori PMSS1 has a multi-cagA genotype, modulating cagA copy number dynamically from zero to four copies. To examine the effect of the immune response on cagA copy number change, we utilized a mouse model with different immune status. PMSS1 recovered from Rag1−/− mice, lacking functional T or B cells, retained more cagA copies. PMSS1 recovered from Il10−/− mice, showing intense inflammation, had fewer cagA copies compared to those recovered from wild-type mice. Moreover, cagA copy number of PMSS1 recovered from wild-type and Il10−/− mice was positively correlated with the capacity to induce IL-8 secretion at four weeks of infection. Since recombination in cagY influences T4SS function, including CagA translocation and IL-8 induction, we constructed a multiple linear regression model to predict H. pylori-induced IL-8 expression based on cagA copy number and cagY recombination status; H. pylori induces more IL-8 secretion when the strain has more cagA copies and intact cagY. This study shows that H. pylori PMSS1 in mice with less intense immune response possess higher cagA copy number than those infected in mice with more intense immune response and thus the multi-cagA genotype, along with cagY recombination, functions as an immune-sensitive regulator of H. pylori virulence.https://www.tandfonline.com/doi/10.1080/19490976.2022.2044721Helicobacter pyloricagAcagYvirulenceimmune response |
| spellingShingle | Sungil Jang Lori M. Hansen Hanfu Su Jay V. Solnick Jeong-Heon Cha Host immune response mediates changes in cagA copy number and virulence potential of Helicobacter pylori Gut Microbes Helicobacter pylori cagA cagY virulence immune response |
| title | Host immune response mediates changes in cagA copy number and virulence potential of Helicobacter pylori |
| title_full | Host immune response mediates changes in cagA copy number and virulence potential of Helicobacter pylori |
| title_fullStr | Host immune response mediates changes in cagA copy number and virulence potential of Helicobacter pylori |
| title_full_unstemmed | Host immune response mediates changes in cagA copy number and virulence potential of Helicobacter pylori |
| title_short | Host immune response mediates changes in cagA copy number and virulence potential of Helicobacter pylori |
| title_sort | host immune response mediates changes in caga copy number and virulence potential of helicobacter pylori |
| topic | Helicobacter pylori cagA cagY virulence immune response |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2044721 |
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