Details

Autor(en) / Beteiligte

• 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, 2nd, 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

Titel

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

Ist Teil von

• Nature immunology, 2021-07, Vol.22 (7), p.839

Ort / Verlag

United States

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.