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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
Authors: 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
Contributors: Massachusetts Institute of Technology. Department of Biological Engineering
Source: PMC
Publisher Information: Springer Science and Business Media LLC
Publication Year: 2023
Collection: DSpace@MIT (Massachusetts Institute of Technology)
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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: Nature Immunology; 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).
Availability: https://hdl.handle.net/1721.1/147779
Rights: Creative Commons Attribution-Noncommercial-Share Alike ; http://creativecommons.org/licenses/by-nc-sa/4.0/
Accession Number: edsbas.296F3B10
Database: BASE