A Functional Role for Antibodies in Tuberculosis
While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Elsevier
2018
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| Online Access: | http://hdl.handle.net/1721.1/117692 https://orcid.org/0000-0002-0050-989X |
| _version_ | 1826211476509032448 |
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| author | Lu, Lenette L. Chung, Amy W. Rosebrock, Tracy R. Ghebremichael, Musie Grace, Patricia S. Schoen, Matthew K. Tafesse, Fikadu Martin, Constance Leung, Vivian Mahan, Alison E. Sips, Magdalena Kumar, Manu P. Tedesco, Jacquelynne Robinson, Hannah Tkachenko, Elizabeth Draghi, Monia Freedberg, Katherine J. Streeck, Hendrik Suscovich, Todd J. Restrepo, Blanca I. Day, Cheryl Fortune, Sarah M. Alter, Galit Yu, Wen-Han Lauffenburger, Douglas A |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Lu, Lenette L. Chung, Amy W. Rosebrock, Tracy R. Ghebremichael, Musie Grace, Patricia S. Schoen, Matthew K. Tafesse, Fikadu Martin, Constance Leung, Vivian Mahan, Alison E. Sips, Magdalena Kumar, Manu P. Tedesco, Jacquelynne Robinson, Hannah Tkachenko, Elizabeth Draghi, Monia Freedberg, Katherine J. Streeck, Hendrik Suscovich, Todd J. Restrepo, Blanca I. Day, Cheryl Fortune, Sarah M. Alter, Galit Yu, Wen-Han Lauffenburger, Douglas A |
| author_sort | Lu, Lenette L. |
| collection | MIT |
| description | While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcγRIII, and distinct Ab glycosylation patterns. Moreover, compared to Abs from Atb, Abs from Ltb drove enhanced phagolysosomal maturation, inflammasome activation, and, most importantly, macrophage killing of intracellular Mtb. Combined, these data point to a potential role for Fc-mediated Ab effector functions, tuned via differential glycosylation, in Mtb control. |
| first_indexed | 2024-09-23T15:06:32Z |
| format | Article |
| id | mit-1721.1/117692 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:06:32Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1176922022-10-02T00:39:46Z A Functional Role for Antibodies in Tuberculosis Lu, Lenette L. Chung, Amy W. Rosebrock, Tracy R. Ghebremichael, Musie Grace, Patricia S. Schoen, Matthew K. Tafesse, Fikadu Martin, Constance Leung, Vivian Mahan, Alison E. Sips, Magdalena Kumar, Manu P. Tedesco, Jacquelynne Robinson, Hannah Tkachenko, Elizabeth Draghi, Monia Freedberg, Katherine J. Streeck, Hendrik Suscovich, Todd J. Restrepo, Blanca I. Day, Cheryl Fortune, Sarah M. Alter, Galit Yu, Wen-Han Lauffenburger, Douglas A Massachusetts Institute of Technology. Department of Biological Engineering Yu, Wen-Han Lauffenburger, Douglas A While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcγRIII, and distinct Ab glycosylation patterns. Moreover, compared to Abs from Atb, Abs from Ltb drove enhanced phagolysosomal maturation, inflammasome activation, and, most importantly, macrophage killing of intracellular Mtb. Combined, these data point to a potential role for Fc-mediated Ab effector functions, tuned via differential glycosylation, in Mtb control. 2018-09-10T19:14:46Z 2018-09-10T19:14:46Z 2016-09 2016-05 2018-09-10T14:15:02Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/117692 Lu, Lenette L. et al. “A Functional Role for Antibodies in Tuberculosis.” Cell 167, 2 (October 2016): 433–443 © 2016 Elsevier Inc https://orcid.org/0000-0002-0050-989X http://dx.doi.org/10.1016/J.CELL.2016.08.072 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Lu, Lenette L. Chung, Amy W. Rosebrock, Tracy R. Ghebremichael, Musie Grace, Patricia S. Schoen, Matthew K. Tafesse, Fikadu Martin, Constance Leung, Vivian Mahan, Alison E. Sips, Magdalena Kumar, Manu P. Tedesco, Jacquelynne Robinson, Hannah Tkachenko, Elizabeth Draghi, Monia Freedberg, Katherine J. Streeck, Hendrik Suscovich, Todd J. Restrepo, Blanca I. Day, Cheryl Fortune, Sarah M. Alter, Galit Yu, Wen-Han Lauffenburger, Douglas A A Functional Role for Antibodies in Tuberculosis |
| title | A Functional Role for Antibodies in Tuberculosis |
| title_full | A Functional Role for Antibodies in Tuberculosis |
| title_fullStr | A Functional Role for Antibodies in Tuberculosis |
| title_full_unstemmed | A Functional Role for Antibodies in Tuberculosis |
| title_short | A Functional Role for Antibodies in Tuberculosis |
| title_sort | functional role for antibodies in tuberculosis |
| url | http://hdl.handle.net/1721.1/117692 https://orcid.org/0000-0002-0050-989X |
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