02037nas a2200373   4500000000100000008004100001260004400042653001500086100000900101700001400110700001400124700001500138700002400153700001300177700001200190700000900202700001700211700001200228700001300240700001300253700002600266700001700292700001300309700001400322700001300336700001800349700001700367700001400384245009600398300001200494490000700506520112500513022002501638       2021                            d  bSpringer Science and Business Media LLC10aImmunology1 aMa F1 aHughes TK1 aTeles RMB1 aAndrade PR1 ade Andrade Silva BJ1 aPlazyo O1 aTsoi LC1 aDo T1 aWadsworth MH1 aOulee A1 aOchoa MT1 aSarno EN1 aLuisa Iruela-Arispe M1 aKlechevsky E1 aBryson B1 aShalek AK1 aBloom BR1 aGudjonsson JE1 aPellegrini M1 aModlin RL00aThe cellular architecture of the antimicrobial response network in human leprosy granulomas  a839-8500 v223 aGranulomas 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.  a1529-2908, 1529-2916