Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis
Tuberculosis is the leading cause of death by an infectious disease worldwide¹. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of par...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science+Business Media
2020
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| Online Access: | https://hdl.handle.net/1721.1/123652 |
| _version_ | 1826203495541243904 |
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| author | Ardain, Amanda Domingo-Gonzalez, Racquel Das, Shibali Kazer, Samuel Weisgurt Howard, Nicole C. Singh, Alveera Ahmed, Mushtaq Nhamoyebonde, Shepherd Rangel-Moreno, Javier Ogongo, Paul Lu, Lan Ramsuran, Duran de la Luz Garcia-Hernandez, Maria K. Ulland, Tyler Darby, Matthew Park, Eugene Karim, Farina Melocchi, Laura Madansein, Rajhmun Dullabh, Kaylesh Jay Dunlap, Micah Marin-Agudelo, Nancy Ebihara, Takashi Ndung’u, Thumbi Kaushal, Deepak Pym, Alexander S. Kolls, Jay K. Steyn, Adrie Zuniga, Joaquin Horsnell, William Yokoyama, Wayne M. Shalek, Alexander K Kloverpris, Henrik N. Colonna, Marco Leslie, Alasdair Khader, Shabaana A. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Ardain, Amanda Domingo-Gonzalez, Racquel Das, Shibali Kazer, Samuel Weisgurt Howard, Nicole C. Singh, Alveera Ahmed, Mushtaq Nhamoyebonde, Shepherd Rangel-Moreno, Javier Ogongo, Paul Lu, Lan Ramsuran, Duran de la Luz Garcia-Hernandez, Maria K. Ulland, Tyler Darby, Matthew Park, Eugene Karim, Farina Melocchi, Laura Madansein, Rajhmun Dullabh, Kaylesh Jay Dunlap, Micah Marin-Agudelo, Nancy Ebihara, Takashi Ndung’u, Thumbi Kaushal, Deepak Pym, Alexander S. Kolls, Jay K. Steyn, Adrie Zuniga, Joaquin Horsnell, William Yokoyama, Wayne M. Shalek, Alexander K Kloverpris, Henrik N. Colonna, Marco Leslie, Alasdair Khader, Shabaana A. |
| author_sort | Ardain, Amanda |
| collection | MIT |
| description | Tuberculosis is the leading cause of death by an infectious disease worldwide¹. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of participants with pulmonary tuberculosis and restored upon treatment. Tuberculosis increased accumulation of ILC subsets in the human lung, coinciding with a robust transcriptional response to infection, including a role in orchestrating the recruitment of immune subsets. Using mouse models, we show that group 3 ILCs (ILC3s) accumulated rapidly in Mtb-infected lungs and coincided with the accumulation of alveolar macrophages. Notably, mice that lacked ILC3s exhibited a reduction in the accumulation of early alveolar macrophages and decreased Mtb control. We show that the C-X-C motif chemokine receptor 5 (CXCR5)–C-X-C motif chemokine ligand 13 (CXCL13) axis is involved in Mtb control, as infection upregulates CXCR5 on circulating ILC3s and increases plasma levels of its ligand, CXCL13, in humans. Moreover, interleukin-23-dependent expansion of ILC3s in mice and production of interleukin-17 and interleukin-22 were found to be critical inducers of lung CXCL13, early innate immunity and the formation of protective lymphoid follicles within granulomas. Thus, we demonstrate an early protective role for ILC3s in immunity to Mtb infection. Keywords: Innate lymphoid cells; Tuberculosis |
| first_indexed | 2024-09-23T12:37:57Z |
| format | Article |
| id | mit-1721.1/123652 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:37:57Z |
| publishDate | 2020 |
| publisher | Springer Science+Business Media |
| record_format | dspace |
| spelling | mit-1721.1/1236522022-10-01T10:10:43Z Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis Ardain, Amanda Domingo-Gonzalez, Racquel Das, Shibali Kazer, Samuel Weisgurt Howard, Nicole C. Singh, Alveera Ahmed, Mushtaq Nhamoyebonde, Shepherd Rangel-Moreno, Javier Ogongo, Paul Lu, Lan Ramsuran, Duran de la Luz Garcia-Hernandez, Maria K. Ulland, Tyler Darby, Matthew Park, Eugene Karim, Farina Melocchi, Laura Madansein, Rajhmun Dullabh, Kaylesh Jay Dunlap, Micah Marin-Agudelo, Nancy Ebihara, Takashi Ndung’u, Thumbi Kaushal, Deepak Pym, Alexander S. Kolls, Jay K. Steyn, Adrie Zuniga, Joaquin Horsnell, William Yokoyama, Wayne M. Shalek, Alexander K Kloverpris, Henrik N. Colonna, Marco Leslie, Alasdair Khader, Shabaana A. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Chemistry Ragon Institute of MGH, MIT and Harvard Broad Institute of MIT and Harvard Koch Institute for Integrative Cancer Research at MIT Tuberculosis is the leading cause of death by an infectious disease worldwide¹. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of participants with pulmonary tuberculosis and restored upon treatment. Tuberculosis increased accumulation of ILC subsets in the human lung, coinciding with a robust transcriptional response to infection, including a role in orchestrating the recruitment of immune subsets. Using mouse models, we show that group 3 ILCs (ILC3s) accumulated rapidly in Mtb-infected lungs and coincided with the accumulation of alveolar macrophages. Notably, mice that lacked ILC3s exhibited a reduction in the accumulation of early alveolar macrophages and decreased Mtb control. We show that the C-X-C motif chemokine receptor 5 (CXCR5)–C-X-C motif chemokine ligand 13 (CXCL13) axis is involved in Mtb control, as infection upregulates CXCR5 on circulating ILC3s and increases plasma levels of its ligand, CXCL13, in humans. Moreover, interleukin-23-dependent expansion of ILC3s in mice and production of interleukin-17 and interleukin-22 were found to be critical inducers of lung CXCL13, early innate immunity and the formation of protective lymphoid follicles within granulomas. Thus, we demonstrate an early protective role for ILC3s in immunity to Mtb infection. Keywords: Innate lymphoid cells; Tuberculosis National Institute of Health (U.S.). (5U24AI118672) 2020-01-23T18:58:55Z 2020-01-23T18:58:55Z 2019-06 2018-05 2020-01-08T13:44:15Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 https://hdl.handle.net/1721.1/123652 Ardain, Amanda et al. "Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis." Nature, 570 (June 2019): 528-532 © 2019, The Author(s), under exclusive licence to Springer Nature Limited. en https://doi.org/10.1038/s41586-019-1276-2 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science+Business Media PMC |
| spellingShingle | Ardain, Amanda Domingo-Gonzalez, Racquel Das, Shibali Kazer, Samuel Weisgurt Howard, Nicole C. Singh, Alveera Ahmed, Mushtaq Nhamoyebonde, Shepherd Rangel-Moreno, Javier Ogongo, Paul Lu, Lan Ramsuran, Duran de la Luz Garcia-Hernandez, Maria K. Ulland, Tyler Darby, Matthew Park, Eugene Karim, Farina Melocchi, Laura Madansein, Rajhmun Dullabh, Kaylesh Jay Dunlap, Micah Marin-Agudelo, Nancy Ebihara, Takashi Ndung’u, Thumbi Kaushal, Deepak Pym, Alexander S. Kolls, Jay K. Steyn, Adrie Zuniga, Joaquin Horsnell, William Yokoyama, Wayne M. Shalek, Alexander K Kloverpris, Henrik N. Colonna, Marco Leslie, Alasdair Khader, Shabaana A. Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis |
| title | Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis |
| title_full | Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis |
| title_fullStr | Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis |
| title_full_unstemmed | Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis |
| title_short | Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis |
| title_sort | group 3 innate lymphoid cells mediate early protective immunity against tuberculosis |
| url | https://hdl.handle.net/1721.1/123652 |
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