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.

肉芽肿是复杂的细胞结构，主要由巨噬细胞和淋巴细胞组成，其功能是遏制和杀死入侵的病原体。在这里，我们通过对麻风活检标本应用单细胞和空间测序来研究与人类麻风肉芽肿中抗菌反应相关的单细胞表型。我们重点关注逆转反应（RR），这是一个动态过程，一些播散性麻风病（L-lep）患者转变为自限性结核性麻风病（T-lep），产生有效的抗菌反应。我们鉴定了一组编码参与抗菌反应的蛋白质的基因，这些蛋白质在 RR 与 L-lep 病变中差异表达，并受干扰素 γ 和白细胞介素 1β 调节。