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The cellular architecture of the antimicrobial response network in human leprosy granulomas.
Ma, Feiyang; Hughes, Travis K; Teles, Rosane M B; 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.
Afiliación
  • Ma F; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • Hughes TK; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, USA.
  • Teles RMB; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
  • Andrade PR; Institute for Medical Engineering & Science and Department of Chemistry, MIT, Cambridge, MA, USA.
  • de Andrade Silva BJ; Department of Immunology, Harvard Medical School, Boston, MA, USA.
  • Plazyo O; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Tsoi LC; Ragon Institute of Massachusetts General Hospital MIT and Harvard, Cambridge, MA, USA.
  • Do T; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • Wadsworth MH; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • Oulee A; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • Ochoa MT; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
  • Sarno EN; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
  • Iruela-Arispe ML; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • Klechevsky E; Institute for Medical Engineering & Science and Department of Chemistry, MIT, Cambridge, MA, USA.
  • Bryson B; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Shalek AK; Ragon Institute of Massachusetts General Hospital MIT and Harvard, Cambridge, MA, USA.
  • Bloom BR; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • Gudjonsson JE; Department of Dermatology, University of Southern California, Los Angeles, CA, USA.
  • Pellegrini M; Leprosy Laboratory, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
  • Modlin RL; Department of Cell and Developmental Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Nat Immunol ; 22(7): 839-850, 2021 07.
Article en En | MEDLINE | ID: mdl-34168371
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-1ß. 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Lepra Lepromatosa / Lepra Tuberculoide / Mycobacterium leprae Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piel / Lepra Lepromatosa / Lepra Tuberculoide / Mycobacterium leprae Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos