Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice
Many antigens from Mycobacterium tuberculosis (M. tuberculosis) have been demonstrated as strong immunogens and proved to have application potential as vaccine candidate antigens. Cyclic di-AMP (c-di-AMP) as a bacterial second messenger regulates various bacterial processes as well as the host immun...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.871135/full |
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| author | Yanzhi Lu Huanhuan Ning Jian Kang Guangchun Bai Lei Zhou Yali Kang Zhengfeng Wu Maolin Tian Junhao Zhao Yueyun Ma Yueyun Ma Yinlan Bai |
| author_facet | Yanzhi Lu Huanhuan Ning Jian Kang Guangchun Bai Lei Zhou Yali Kang Zhengfeng Wu Maolin Tian Junhao Zhao Yueyun Ma Yueyun Ma Yinlan Bai |
| author_sort | Yanzhi Lu |
| collection | DOAJ |
| description | Many antigens from Mycobacterium tuberculosis (M. tuberculosis) have been demonstrated as strong immunogens and proved to have application potential as vaccine candidate antigens. Cyclic di-AMP (c-di-AMP) as a bacterial second messenger regulates various bacterial processes as well as the host immune responses. Rv2837c, the c-di-AMP phosphodiesterase (CnpB), was found to be relative to virulence of M. tuberculosis and interference with host innate immune response. In this study, recombinant CnpB was administered subcutaneously to mice. We found that CnpB had strong immunogenicity and induced high levels of humoral response and lung mucosal immunity after M. tuberculosis intranasally infection. CnpB immunization stimulated splenocyte proliferation and the increasing number of activated NK cells but had little effects on Th1/Th2 cellular immune responses in spleens. However, CnpB induced significant Th1/Th2 cellular immune responses with a decreased number of T and B cells in the lungs, and significantly recruits of CD4+ and CD8+ T cells after M. tuberculosis attenuated strain H37Ra infection. Besides, we first reported that CnpB could stimulate IFN-β expression transitorily and inhibit the autophagy of macrophages in vitro. In mice intranasally infection model, CnpB immunization alleviated pathological changes and reduced M. tuberculosis H37Ra loads in the lungs. Thus, our results suggested that CnpB interferes with host innate and adaptive immune responses and confers protection against M. tuberculosis respiratory infection, which should be considered in vaccine development as well as a drug target. |
| first_indexed | 2024-04-12T13:56:58Z |
| format | Article |
| id | doaj.art-5e7c875a7670440ebed169c4e1693b9a |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-12T13:56:58Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-5e7c875a7670440ebed169c4e1693b9a2022-12-22T03:30:20ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-06-011210.3389/fcimb.2022.871135871135Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in MiceYanzhi Lu0Huanhuan Ning1Jian Kang2Guangchun Bai3Lei Zhou4Yali Kang5Zhengfeng Wu6Maolin Tian7Junhao Zhao8Yueyun Ma9Yueyun Ma10Yinlan Bai11Department of Microbiology and Pathogen Biology, Basic Medical School, Air Force Medical University, Xi’an, ChinaDepartment of Microbiology and Pathogen Biology, Basic Medical School, Air Force Medical University, Xi’an, ChinaDepartment of Microbiology and Pathogen Biology, Basic Medical School, Air Force Medical University, Xi’an, ChinaDepartment of Immunology and Microbial Disease, Albany Medical College, Albany, NY, United StatesDepartment of Clinical Laboratory, The First Affiliated Hospital, Air Force Medical University, Xi’an, ChinaDepartment of Physiology, Basic Medical School, Ningxia Medical University, Yinchuan, ChinaStudent Brigade, Basic Medical School, Air Force Medical University, Xi’an, ChinaStudent Brigade, Basic Medical School, Air Force Medical University, Xi’an, ChinaStudent Brigade, Basic Medical School, Air Force Medical University, Xi’an, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital, Air Force Medical University, Xi’an, ChinaDepartment of Clinical Laboratory, Air Force Medical Center, Air Force Medical University, Beijing, ChinaDepartment of Microbiology and Pathogen Biology, Basic Medical School, Air Force Medical University, Xi’an, ChinaMany antigens from Mycobacterium tuberculosis (M. tuberculosis) have been demonstrated as strong immunogens and proved to have application potential as vaccine candidate antigens. Cyclic di-AMP (c-di-AMP) as a bacterial second messenger regulates various bacterial processes as well as the host immune responses. Rv2837c, the c-di-AMP phosphodiesterase (CnpB), was found to be relative to virulence of M. tuberculosis and interference with host innate immune response. In this study, recombinant CnpB was administered subcutaneously to mice. We found that CnpB had strong immunogenicity and induced high levels of humoral response and lung mucosal immunity after M. tuberculosis intranasally infection. CnpB immunization stimulated splenocyte proliferation and the increasing number of activated NK cells but had little effects on Th1/Th2 cellular immune responses in spleens. However, CnpB induced significant Th1/Th2 cellular immune responses with a decreased number of T and B cells in the lungs, and significantly recruits of CD4+ and CD8+ T cells after M. tuberculosis attenuated strain H37Ra infection. Besides, we first reported that CnpB could stimulate IFN-β expression transitorily and inhibit the autophagy of macrophages in vitro. In mice intranasally infection model, CnpB immunization alleviated pathological changes and reduced M. tuberculosis H37Ra loads in the lungs. Thus, our results suggested that CnpB interferes with host innate and adaptive immune responses and confers protection against M. tuberculosis respiratory infection, which should be considered in vaccine development as well as a drug target.https://www.frontiersin.org/articles/10.3389/fcimb.2022.871135/fullMycobacterium tuberculosiscyclic-di-AMPphosphodiesteraseimmune responseinfectionvaccine |
| spellingShingle | Yanzhi Lu Huanhuan Ning Jian Kang Guangchun Bai Lei Zhou Yali Kang Zhengfeng Wu Maolin Tian Junhao Zhao Yueyun Ma Yueyun Ma Yinlan Bai Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice Frontiers in Cellular and Infection Microbiology Mycobacterium tuberculosis cyclic-di-AMP phosphodiesterase immune response infection vaccine |
| title | Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice |
| title_full | Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice |
| title_fullStr | Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice |
| title_full_unstemmed | Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice |
| title_short | Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice |
| title_sort | cyclic di amp phosphodiesterase elicits protective immune responses against mycobacterium tuberculosis h37ra infection in mice |
| topic | Mycobacterium tuberculosis cyclic-di-AMP phosphodiesterase immune response infection vaccine |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.871135/full |
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