RT Journal Article
SR Electronic
T1 Single Cell and Spatial Transcriptomics Defines the Cellular Architecture of the Antimicrobial Response Network in Human Leprosy Granulomas
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.01.406819
DO 10.1101/2020.12.01.406819
A1 Feiyang Ma
A1 Travis K. Hughes
A1 Rosane M.B. Teles
A1 Priscila R. Andrade
A1 Bruno J. de Andrade Silva
A1 Olesya Plazyo
A1 Lam C. Tsoi
A1 Tran Do
A1 Marc H Wadsworth II
A1 Aislyn Oulee
A1 Maria Teresa Ochoa
A1 Euzenir N. Sarno
A1 M. Luisa Iruela-Arispe
A1 Bryan Bryson
A1 Alex K. Shalek
A1 Barry R. Bloom
A1 Johann E. Gudjonsson
A1 Matteo Pellegrini
A1 Robert L. Modlin
YR 2020
UL http://biorxiv.org/content/early/2020/12/02/2020.12.01.406819.abstract
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.