The cellular architecture of the antimicrobial response network in human leprosy granulomas
| Autor: | Priscila Ribeiro Andrade, Matteo Pellegrini, Johann E. Gudjonsson, Robert L. Modlin, Alex K. Shalek, Aislyn Oulee, Euzenir Nunes Sarno, Barry R. Bloom, Eynav Klechevsky, Tran Do, Bryan D. Bryson, Bruno Jorge de Andrade Silva, M. Luisa Iruela-Arispe, Olesya Plazyo, Maria Teresa Ochoa, Rosane M. B. Teles, Marc H. Wadsworth, Lam C. Tsoi, Feiyang Ma, Travis K. Hughes |
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| Rok vydání: | 2021 |
| Předmět: |
Keratinocytes
Male 0301 basic medicine Tuberculoid T-Lymphocytes Tuberculoid leprosy 0302 clinical medicine Lepromatous Gene expression 2.1 Biological and endogenous factors Immunology and Allergy RNA-Seq Aetiology Skin Lepromatous leprosy Granuloma medicine.diagnostic_test Middle Aged Antimicrobial Leprosy Tuberculoid Research Highlight Phenotype Leprosy Lepromatous Mycobacterium leprae Infectious Diseases Host-Pathogen Interactions Female Leprosy Single-Cell Analysis Adult Cell type Adolescent Immunology Biology Article 03 medical and health sciences Clinical Research Biopsy Genetics medicine Humans Aged Macrophages Gene Expression Profiling Fibroblasts medicine.disease Good Health and Well Being 030104 developmental biology Transcriptome 030215 immunology |
| Zdroj: | Nat Immunol Nature immunology, vol 22, iss 7 Cell Mol Immunol |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/s41590-021-00956-8 |
| Popis: | 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. Modlin and colleagues examined the skin lesions of human leprosy patients using single-cell RNA sequencing coupled to cellular spatial mapping. Their analysis maps the architecture of granulomas in leprosy lesions from patients with leprosy with localized disease (tuberculoid leprosy, reversal reaction) to those with progressive infection (lepromatous leprosy). |
| Databáze: | OpenAIRE |
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