Single cell and spatial transcriptomics defines the cellular architecture of the antimicrobial response network in human leprosy granulomas

Biology Biology
Cell Atlas Cell Atlas
Genomics Genomics
Immunology Immunology
Infectious Disease Infectious Disease
Alex K. Shalek Alex K. Shalek
Marc Wadsworth II Marc Wadsworth II
Travis Hughes Travis Hughes

Ma et al.▾ Ma, F., Hughes, T.K., Teles, R.M.B., Andrade, P.R., de Andrade Silva, B.J., Plazyo, O., Tsoi, L.C., Do, T., Wadsworth II, M.H., Oulee, A., Ochoa, M.T., Sarno, E.N., Iruela-Arispe, M.L., Bryson, B., Shalek, A.K., Bloom, B.R., Gudjonsson, J.E., Pellegrini, M., Modlin, R.L.

bioRxiv

December, 2020

Abstract

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.