Single Cell and Spatial Transcriptomics Defines the Cellular Architecture of the Antimicrobial Response Network in Human Leprosy Granulomas

Overview

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-g and IL-1b. 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.

Scripts and R data files

We share the scripts and R data files used to generate the figures for the manuscript.
The codes are implemented in vignettes to show the results of running these scripts. The Vignettes are saved in the "Vignettes" folder as html files. These html files can be downloaded to local computer as viewed as offline websites.
The R scripts are saved in the "Rscripts" folder. The R data files can be downloaded here.

Examples

Below is an example showing the beggning of the vignette used to generate the plots with all the cells in the scRNA-seq dataset.