@article{95651, keywords = {Immunology}, author = {Ma F and Hughes TK and Teles RMB and Andrade PR and de Andrade Silva BJ and Plazyo O and Tsoi LC and Do T and Wadsworth MH and Oulee A and Ochoa MT and Sarno EN and Luisa Iruela-Arispe M and Klechevsky E and Bryson B and Shalek AK and Bloom BR and Gudjonsson JE and Pellegrini M and Modlin RL}, title = {The cellular architecture of the antimicrobial response network in human leprosy granulomas}, abstract = {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.}, year = {2021}, journal = {Nature Immunology}, volume = {22}, pages = {839-850}, publisher = {Springer Science and Business Media LLC}, issn = {1529-2908, 1529-2916}, doi = {10.1038/s41590-021-00956-8}, language = {eng}, }