The cellular architecture of the antimicrobial response network in human leprosy granulomas

Feiyang Ma, Travis K. Hughes, Rosane M.B. Teles, Priscila R. Andrade, Bruno J. de Andrade Silva, Olesya Plazyo, Lam C. Tsoi, Tran Do, Marc H. Wadsworth, Aislyn Oulee, Maria Teresa Ochoa, Euzenir N. Sarno, M. Luisa Iruela-Arispe, Eynav Klechevsky, Bryan Bryson, Alex K. Shalek, Barry R. Bloom, Johann E. Gudjonsson, Matteo Pellegrini, Robert L. Modlin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)839-850
Number of pages12
JournalNature Immunology
Volume22
Issue number7
DOIs
StatePublished - Jul 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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