PT  - JOURNAL ARTICLE
AU  - Feiyang Ma
AU  - Travis K. Hughes
AU  - Rosane M.B. Teles
AU  - Priscila R. Andrade
AU  - Bruno J. de Andrade Silva
AU  - Olesya Plazyo
AU  - Lam C. Tsoi
AU  - Tran Do
AU  - Marc H Wadsworth II
AU  - Aislyn Oulee
AU  - Maria Teresa Ochoa
AU  - Euzenir N. Sarno
AU  - M. Luisa Iruela-Arispe
AU  - Bryan Bryson
AU  - Alex K. Shalek
AU  - Barry R. Bloom
AU  - Johann E. Gudjonsson
AU  - Matteo Pellegrini
AU  - Robert L. Modlin
TI  - Single Cell and Spatial Transcriptomics Defines the Cellular Architecture of the Antimicrobial Response Network in Human Leprosy Granulomas
AID  - 10.1101/2020.12.01.406819
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.01.406819
4099  - http://biorxiv.org/content/early/2020/12/02/2020.12.01.406819.short
4100  - http://biorxiv.org/content/early/2020/12/02/2020.12.01.406819.full
AB  - Granulomas are complex cellular structures comprised predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated 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 (RR), a dynamic process in which some patients with disseminated lepromatous leprosy (L-lep) transition towards 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 IFN-γ and IL-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 contribute to the antimicrobial response.Competing Interest StatementA.K.S. reports compensation for consulting and/or SAB membership from Merck, Honeycomb Biotechnologies, Cellarity, Cogen Therapeutics, Orche Bio, and Dahlia Biosciences.