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Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis
Mycobacterium tuberculosis (Mtb) exposure drives antibody responses, but whether patients with active tuberculosis elicit protective antibodies, and against which antigens, is still unclear. Here we generate monoclonal antibodies from memory B cells of one patient to investigate the B cell responses...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840946/ https://www.ncbi.nlm.nih.gov/pubmed/33504803 http://dx.doi.org/10.1038/s41467-021-20930-0 |
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author | Watson, Avia Li, Hao Ma, Bingting Weiss, Ronen Bendayan, Daniele Abramovitz, Lilach Ben-Shalom, Noam Mor, Michael Pinko, Erica Bar Oz, Michal Wang, Zhenqi Du, Fengjiao Lu, Yu Rybniker, Jan Dahan, Rony Huang, Hairong Barkan, Daniel Xiang, Ye Javid, Babak Freund, Natalia T. |
author_facet | Watson, Avia Li, Hao Ma, Bingting Weiss, Ronen Bendayan, Daniele Abramovitz, Lilach Ben-Shalom, Noam Mor, Michael Pinko, Erica Bar Oz, Michal Wang, Zhenqi Du, Fengjiao Lu, Yu Rybniker, Jan Dahan, Rony Huang, Hairong Barkan, Daniel Xiang, Ye Javid, Babak Freund, Natalia T. |
author_sort | Watson, Avia |
collection | PubMed |
description | Mycobacterium tuberculosis (Mtb) exposure drives antibody responses, but whether patients with active tuberculosis elicit protective antibodies, and against which antigens, is still unclear. Here we generate monoclonal antibodies from memory B cells of one patient to investigate the B cell responses during active infection. The antibodies, members of four distinct B cell clones, are directed against the Mtb phosphate transporter subunit PstS1. Antibodies p4-36 and p4-163 reduce Mycobacterium bovis-BCG and Mtb levels in an ex vivo human whole blood growth inhibition assay in an FcR-dependent manner; meanwhile, germline versions of p4-36 and p4-163 do not bind Mtb. Crystal structures of p4-36 and p4-170, complexed to PstS1, are determined at 2.1 Å and 2.4 Å resolution, respectively, to reveal two distinctive PstS1 epitopes. Lastly, a prophylactic p4-36 and p4-163 treatment in Mtb-infected Balb/c mice reduces bacterial lung burden by 50%. Our study shows that inhibitory anti-PstS1 B cell responses arise during active tuberculosis. |
format | Online Article Text |
id | pubmed-7840946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78409462021-02-08 Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis Watson, Avia Li, Hao Ma, Bingting Weiss, Ronen Bendayan, Daniele Abramovitz, Lilach Ben-Shalom, Noam Mor, Michael Pinko, Erica Bar Oz, Michal Wang, Zhenqi Du, Fengjiao Lu, Yu Rybniker, Jan Dahan, Rony Huang, Hairong Barkan, Daniel Xiang, Ye Javid, Babak Freund, Natalia T. Nat Commun Article Mycobacterium tuberculosis (Mtb) exposure drives antibody responses, but whether patients with active tuberculosis elicit protective antibodies, and against which antigens, is still unclear. Here we generate monoclonal antibodies from memory B cells of one patient to investigate the B cell responses during active infection. The antibodies, members of four distinct B cell clones, are directed against the Mtb phosphate transporter subunit PstS1. Antibodies p4-36 and p4-163 reduce Mycobacterium bovis-BCG and Mtb levels in an ex vivo human whole blood growth inhibition assay in an FcR-dependent manner; meanwhile, germline versions of p4-36 and p4-163 do not bind Mtb. Crystal structures of p4-36 and p4-170, complexed to PstS1, are determined at 2.1 Å and 2.4 Å resolution, respectively, to reveal two distinctive PstS1 epitopes. Lastly, a prophylactic p4-36 and p4-163 treatment in Mtb-infected Balb/c mice reduces bacterial lung burden by 50%. Our study shows that inhibitory anti-PstS1 B cell responses arise during active tuberculosis. Nature Publishing Group UK 2021-01-27 /pmc/articles/PMC7840946/ /pubmed/33504803 http://dx.doi.org/10.1038/s41467-021-20930-0 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Watson, Avia Li, Hao Ma, Bingting Weiss, Ronen Bendayan, Daniele Abramovitz, Lilach Ben-Shalom, Noam Mor, Michael Pinko, Erica Bar Oz, Michal Wang, Zhenqi Du, Fengjiao Lu, Yu Rybniker, Jan Dahan, Rony Huang, Hairong Barkan, Daniel Xiang, Ye Javid, Babak Freund, Natalia T. Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis |
title | Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis |
title_full | Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis |
title_fullStr | Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis |
title_full_unstemmed | Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis |
title_short | Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis |
title_sort | human antibodies targeting a mycobacterium transporter protein mediate protection against tuberculosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840946/ https://www.ncbi.nlm.nih.gov/pubmed/33504803 http://dx.doi.org/10.1038/s41467-021-20930-0 |
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