Mycobacterial Lipoprotein Z Triggers Efficient Innate and Adaptive Immunity for Protection Against Mycobacterium tuberculosis Infection
Mycobacterial lipoproteins are considered to be involved in both virulence and immunoregulatory processes during Mycobacterium tuberculosis (M.tb) infection. In our previous investigations on the immunoreactivity of more than 30 M.tb proteins in active TB patients, we identified mycobacterial lipopr...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-01-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.03190/full |
id |
doaj-7c31af9859934281885b95d102a7b1c9 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yingying Chen Jia-ni Xiao Yong Li Yang-jiong Xiao Yan-qing Xiong Ying Liu Shu-jun Wang Ping Ji Guo-ping Zhao Hao Shen Hao Shen Shui-hua Lu Xiao-yong Fan Xiao-yong Fan Ying Wang Ying Wang |
spellingShingle |
Yingying Chen Jia-ni Xiao Yong Li Yang-jiong Xiao Yan-qing Xiong Ying Liu Shu-jun Wang Ping Ji Guo-ping Zhao Hao Shen Hao Shen Shui-hua Lu Xiao-yong Fan Xiao-yong Fan Ying Wang Ying Wang Mycobacterial Lipoprotein Z Triggers Efficient Innate and Adaptive Immunity for Protection Against Mycobacterium tuberculosis Infection Frontiers in Immunology lipoprotein Z tuberculosis innate immunity T cell immunity immune protection |
author_facet |
Yingying Chen Jia-ni Xiao Yong Li Yang-jiong Xiao Yan-qing Xiong Ying Liu Shu-jun Wang Ping Ji Guo-ping Zhao Hao Shen Hao Shen Shui-hua Lu Xiao-yong Fan Xiao-yong Fan Ying Wang Ying Wang |
author_sort |
Yingying Chen |
title |
Mycobacterial Lipoprotein Z Triggers Efficient Innate and Adaptive Immunity for Protection Against Mycobacterium tuberculosis Infection |
title_short |
Mycobacterial Lipoprotein Z Triggers Efficient Innate and Adaptive Immunity for Protection Against Mycobacterium tuberculosis Infection |
title_full |
Mycobacterial Lipoprotein Z Triggers Efficient Innate and Adaptive Immunity for Protection Against Mycobacterium tuberculosis Infection |
title_fullStr |
Mycobacterial Lipoprotein Z Triggers Efficient Innate and Adaptive Immunity for Protection Against Mycobacterium tuberculosis Infection |
title_full_unstemmed |
Mycobacterial Lipoprotein Z Triggers Efficient Innate and Adaptive Immunity for Protection Against Mycobacterium tuberculosis Infection |
title_sort |
mycobacterial lipoprotein z triggers efficient innate and adaptive immunity for protection against mycobacterium tuberculosis infection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-01-01 |
description |
Mycobacterial lipoproteins are considered to be involved in both virulence and immunoregulatory processes during Mycobacterium tuberculosis (M.tb) infection. In our previous investigations on the immunoreactivity of more than 30 M.tb proteins in active TB patients, we identified mycobacterial lipoprotein Z (LppZ) as one of the most immune dominant antigens. How LppZ triggers immune responses is still unclear. In this study, we analyzed LppZ-mediated innate and adaptive immunity using a murine air pouch model and an M.tb infection model, respectively. We found that LppZ could not only recruit inflammatory cells but also induce the production of proinflammatory cytokines inside the pouches. LppZ could also induce strong Th1 responses following immunization and confer protection against challenge with M.tb virulent strain H37Rv at a similar level to BCG vaccination but with less pathological damage in the lungs. Furthermore, we revealed the presence of LppZ-specific functional CD4+ T cells in the lungs of the challenged mice that were capable of secreting double or triple cytokines, including IFN-γ, IL-2, and TNF-α. Our study thus demonstrates that LppZ is of strong immunogenicity during M.tb infection in both humans and mice and has the ability to trigger effective innate and cellular immunity. Considering the limitations of candidate antigens in the pipeline of TB vaccine development, LppZ-mediated immune protection against M.tb challenge in the mouse model implies its potential application in vaccine development. |
topic |
lipoprotein Z tuberculosis innate immunity T cell immunity immune protection |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.03190/full |
work_keys_str_mv |
AT yingyingchen mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT jianixiao mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT yongli mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT yangjiongxiao mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT yanqingxiong mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT yingliu mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT shujunwang mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT pingji mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT guopingzhao mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT haoshen mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT haoshen mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT shuihualu mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT xiaoyongfan mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT xiaoyongfan mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT yingwang mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection AT yingwang mycobacteriallipoproteinztriggersefficientinnateandadaptiveimmunityforprotectionagainstmycobacteriumtuberculosisinfection |
_version_ |
1725837130723229696 |
spelling |
doaj-7c31af9859934281885b95d102a7b1c92020-11-24T22:02:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-01-01910.3389/fimmu.2018.03190417303Mycobacterial Lipoprotein Z Triggers Efficient Innate and Adaptive Immunity for Protection Against Mycobacterium tuberculosis InfectionYingying Chen0Jia-ni Xiao1Yong Li2Yang-jiong Xiao3Yan-qing Xiong4Ying Liu5Shu-jun Wang6Ping Ji7Guo-ping Zhao8Hao Shen9Hao Shen10Shui-hua Lu11Xiao-yong Fan12Xiao-yong Fan13Ying Wang14Ying Wang15Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, ChinaKey Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, ChinaDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesKey Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaKey Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaTB Center, Shanghai Emerging and Re-emerging Infectious Disease Institute, Fudan University, Shanghai, ChinaDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, ChinaShanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, ChinaMycobacterial lipoproteins are considered to be involved in both virulence and immunoregulatory processes during Mycobacterium tuberculosis (M.tb) infection. In our previous investigations on the immunoreactivity of more than 30 M.tb proteins in active TB patients, we identified mycobacterial lipoprotein Z (LppZ) as one of the most immune dominant antigens. How LppZ triggers immune responses is still unclear. In this study, we analyzed LppZ-mediated innate and adaptive immunity using a murine air pouch model and an M.tb infection model, respectively. We found that LppZ could not only recruit inflammatory cells but also induce the production of proinflammatory cytokines inside the pouches. LppZ could also induce strong Th1 responses following immunization and confer protection against challenge with M.tb virulent strain H37Rv at a similar level to BCG vaccination but with less pathological damage in the lungs. Furthermore, we revealed the presence of LppZ-specific functional CD4+ T cells in the lungs of the challenged mice that were capable of secreting double or triple cytokines, including IFN-γ, IL-2, and TNF-α. Our study thus demonstrates that LppZ is of strong immunogenicity during M.tb infection in both humans and mice and has the ability to trigger effective innate and cellular immunity. Considering the limitations of candidate antigens in the pipeline of TB vaccine development, LppZ-mediated immune protection against M.tb challenge in the mouse model implies its potential application in vaccine development.https://www.frontiersin.org/article/10.3389/fimmu.2018.03190/fulllipoprotein Ztuberculosisinnate immunityT cell immunityimmune protection |