Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis
Abstract Accumulating evidence from experimental animal models suggests that antibodies play a protective role against tuberculosis (TB). However, little is known about the antibodies generated upon Mycobacterium tuberculosis (MTB) exposure in humans. Here, we performed a molecular and functional ch...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-10-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201606330 |
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| author | Natalie Zimmermann Verena Thormann Bo Hu Anne‐Britta Köhler Aki Imai‐Matsushima Camille Locht Eusondia Arnett Larry S Schlesinger Thomas Zoller Mariana Schürmann Stefan HE Kaufmann Hedda Wardemann |
| author_facet | Natalie Zimmermann Verena Thormann Bo Hu Anne‐Britta Köhler Aki Imai‐Matsushima Camille Locht Eusondia Arnett Larry S Schlesinger Thomas Zoller Mariana Schürmann Stefan HE Kaufmann Hedda Wardemann |
| author_sort | Natalie Zimmermann |
| collection | DOAJ |
| description | Abstract Accumulating evidence from experimental animal models suggests that antibodies play a protective role against tuberculosis (TB). However, little is known about the antibodies generated upon Mycobacterium tuberculosis (MTB) exposure in humans. Here, we performed a molecular and functional characterization of the human B‐cell response to MTB by generating recombinant monoclonal antibodies from single isolated B cells of untreated adult patients with acute pulmonary TB and from MTB‐exposed healthcare workers. The data suggest that the acute plasmablast response to MTB originates from reactivated memory B cells and indicates a mucosal origin. Through functional analyses, we identified MTB inhibitory antibodies against mycobacterial antigens including virulence factors that play important roles in host cell infection. The inhibitory activity of anti‐MTB antibodies was directly linked to their isotype. Monoclonal as well as purified serum IgA antibodies showed MTB blocking activity independently of Fc alpha receptor expression, whereas IgG antibodies promoted the host cell infection. Together, the data provide molecular insights into the human antibody response to MTB and may thereby facilitate the design of protective vaccination strategies. |
| format | Article |
| id | doaj-art-b7388aeba1964598a12b5101a04b9133 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-b7388aeba1964598a12b5101a04b91332025-08-20T03:43:30ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-10-018111325133910.15252/emmm.201606330Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosisNatalie Zimmermann0Verena Thormann1Bo Hu2Anne‐Britta Köhler3Aki Imai‐Matsushima4Camille Locht5Eusondia Arnett6Larry S Schlesinger7Thomas Zoller8Mariana Schürmann9Stefan HE Kaufmann10Hedda Wardemann11Research Group Molecular Immunology, Max Planck Institute for Infection BiologyResearch Group Molecular Immunology, Max Planck Institute for Infection BiologyResearch Group Molecular Immunology, Max Planck Institute for Infection BiologyDepartment of Immunology, Max Planck Institute for Infection BiologyDepartment of Molecular Biology, Max Planck Institute for Infection BiologyU1019 ‐ UMR 8204 ‐ CIIL ‐ Centre for Infection and Immunity of Lille, University of LilleCenter for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State UniversityCenter for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State UniversityDepartment of Infectious Diseases and Respiratory Medicine, Charité University Medical CenterDepartment of Infectious Diseases and Respiratory Medicine, Charité University Medical CenterDepartment of Immunology, Max Planck Institute for Infection BiologyResearch Group Molecular Immunology, Max Planck Institute for Infection BiologyAbstract Accumulating evidence from experimental animal models suggests that antibodies play a protective role against tuberculosis (TB). However, little is known about the antibodies generated upon Mycobacterium tuberculosis (MTB) exposure in humans. Here, we performed a molecular and functional characterization of the human B‐cell response to MTB by generating recombinant monoclonal antibodies from single isolated B cells of untreated adult patients with acute pulmonary TB and from MTB‐exposed healthcare workers. The data suggest that the acute plasmablast response to MTB originates from reactivated memory B cells and indicates a mucosal origin. Through functional analyses, we identified MTB inhibitory antibodies against mycobacterial antigens including virulence factors that play important roles in host cell infection. The inhibitory activity of anti‐MTB antibodies was directly linked to their isotype. Monoclonal as well as purified serum IgA antibodies showed MTB blocking activity independently of Fc alpha receptor expression, whereas IgG antibodies promoted the host cell infection. Together, the data provide molecular insights into the human antibody response to MTB and may thereby facilitate the design of protective vaccination strategies.https://doi.org/10.15252/emmm.201606330antibodiesB cellsinfectionisotypeMycobacterium tuberculosis |
| spellingShingle | Natalie Zimmermann Verena Thormann Bo Hu Anne‐Britta Köhler Aki Imai‐Matsushima Camille Locht Eusondia Arnett Larry S Schlesinger Thomas Zoller Mariana Schürmann Stefan HE Kaufmann Hedda Wardemann Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis EMBO Molecular Medicine antibodies B cells infection isotype Mycobacterium tuberculosis |
| title | Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis |
| title_full | Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis |
| title_fullStr | Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis |
| title_full_unstemmed | Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis |
| title_short | Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis |
| title_sort | human isotype dependent inhibitory antibody responses against mycobacterium tuberculosis |
| topic | antibodies B cells infection isotype Mycobacterium tuberculosis |
| url | https://doi.org/10.15252/emmm.201606330 |
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