01948nas a2200361   4500000000100000008004100001260001200042100000900054700001400063700001300077700001400090700001200104700001300116700001100129700000900140700001600149700001200165700001300177700001200190700002000202700001700222700001300239700001300252700001200265700001700277700001700294700001300311245009700324300001200421490000700433520113200440022001401572       2021                            d  c07/20211 aMa F1 aHughes TK1 aTeles RM1 aAndrade P1 aSilva B1 aPlazyo O1 aTsoi L1 aDo T1 aWadsworth M1 aOulee A1 aOchoa MT1 aSarno E1 aIruela-Arispe L1 aKlechevsky E1 aBryson B1 aShalek A1 aBloom B1 aGudjonsson J1 aPellegrini M1 aModlin R00aThe cellular architecture of the antimicrobial response network in human leprosy granulomas.  a839-8500 v223 a<p>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.</p>  a1529-2916