The cellular architecture of the antimicrobial response network in human leprosy granulomas
Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spat...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/147779 |
| _version_ | 1826209212934389760 |
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| author | Ma, Feiyang Hughes, Travis K Teles, Rosane MB Andrade, Priscila R de Andrade Silva, Bruno J Plazyo, Olesya Tsoi, Lam C Do, Tran Wadsworth, Marc H Oulee, Aislyn Ochoa, Maria Teresa Sarno, Euzenir N Iruela-Arispe, M Luisa Klechevsky, Eynav Bryson, Bryan Shalek, Alex K Bloom, Barry R Gudjonsson, Johann E Pellegrini, Matteo Modlin, Robert L |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Ma, Feiyang Hughes, Travis K Teles, Rosane MB Andrade, Priscila R de Andrade Silva, Bruno J Plazyo, Olesya Tsoi, Lam C Do, Tran Wadsworth, Marc H Oulee, Aislyn Ochoa, Maria Teresa Sarno, Euzenir N Iruela-Arispe, M Luisa Klechevsky, Eynav Bryson, Bryan Shalek, Alex K Bloom, Barry R Gudjonsson, Johann E Pellegrini, Matteo Modlin, Robert L |
| author_sort | Ma, Feiyang |
| collection | MIT |
| description | Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1β. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response. |
| first_indexed | 2024-09-23T14:18:57Z |
| format | Article |
| id | mit-1721.1/147779 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:18:57Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1477792023-02-01T03:18:54Z The cellular architecture of the antimicrobial response network in human leprosy granulomas Ma, Feiyang Hughes, Travis K Teles, Rosane MB Andrade, Priscila R de Andrade Silva, Bruno J Plazyo, Olesya Tsoi, Lam C Do, Tran Wadsworth, Marc H Oulee, Aislyn Ochoa, Maria Teresa Sarno, Euzenir N Iruela-Arispe, M Luisa Klechevsky, Eynav Bryson, Bryan Shalek, Alex K Bloom, Barry R Gudjonsson, Johann E Pellegrini, Matteo Modlin, Robert L Massachusetts Institute of Technology. Department of Biological Engineering Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1β. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response. 2023-01-30T15:10:41Z 2023-01-30T15:10:41Z 2021 2023-01-30T15:00:48Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147779 Ma, Feiyang, Hughes, Travis K, Teles, Rosane MB, Andrade, Priscila R, de Andrade Silva, Bruno J et al. 2021. "The cellular architecture of the antimicrobial response network in human leprosy granulomas." Nature Immunology, 22 (7). en 10.1038/S41590-021-00956-8 Nature Immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Ma, Feiyang Hughes, Travis K Teles, Rosane MB Andrade, Priscila R de Andrade Silva, Bruno J Plazyo, Olesya Tsoi, Lam C Do, Tran Wadsworth, Marc H Oulee, Aislyn Ochoa, Maria Teresa Sarno, Euzenir N Iruela-Arispe, M Luisa Klechevsky, Eynav Bryson, Bryan Shalek, Alex K Bloom, Barry R Gudjonsson, Johann E Pellegrini, Matteo Modlin, Robert L The cellular architecture of the antimicrobial response network in human leprosy granulomas |
| title | The cellular architecture of the antimicrobial response network in human leprosy granulomas |
| title_full | The cellular architecture of the antimicrobial response network in human leprosy granulomas |
| title_fullStr | The cellular architecture of the antimicrobial response network in human leprosy granulomas |
| title_full_unstemmed | The cellular architecture of the antimicrobial response network in human leprosy granulomas |
| title_short | The cellular architecture of the antimicrobial response network in human leprosy granulomas |
| title_sort | cellular architecture of the antimicrobial response network in human leprosy granulomas |
| url | https://hdl.handle.net/1721.1/147779 |
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