The cellular architecture of the antimicrobial response network in human leprosy granulomas
Name
nihms-1749343.pdf
Description
Accepted version
Size
7.73 MB
Format
Adobe PDF
Checksum (MD5)
8b3421063dd91ec1d9e6023512c69d39
Author(s)
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
Date Issued
2021
Journal
Nature Immunology
Publisher
Springer Science and Business Media LLC
Citation
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).
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/S41590-021-00956-8
