中文摘要：

结核分枝杆菌感染后，肺泡巨噬细胞最初被感染，但无效地限制了细菌复制。当主要的感染细胞生态位从肺泡转向单核细胞衍生的巨噬细胞 （MDM） 时，结核分枝杆菌在肺中不同细胞类型中的分布随着 T 细胞免疫的开始而变化。我们假设不同细胞类型之间细菌分布的变化是由感染细胞的 T 细胞识别差异及其随后激活的抗菌效应机制驱动的。我们发现 CD4 和 CD8 T 细胞可有效消除肺泡巨噬细胞中的结核分枝杆菌感染，但它们对抑制 MDM 感染的影响较小，MDM 可能是一个细菌生态位。重要的是，CD4 T 细胞反应增强了 MDM 向肺部的募集。因此，感染的结果取决于 T 细胞亚群和感染细胞之间的相互作用;两者都有助于感染的消退和持续性。

英文摘要：

Following Mycobacterium tuberculosis infection, alveolar macrophages are initially infected but ineffectively restrict bacterial replication. The distribution of M. tuberculosis among different cell types in the lung changes with the onset of T cell immunity when the dominant infected cellular niche shifts from alveolar to monocyte-derived macrophages (MDM). We hypothesize that changes in bacterial distribution among different cell types is driven by differences in T cell recognition of infected cells and their subsequent activation of antimicrobial effector mechanisms. We show that CD4 and CD8 T cells efficiently eliminate M. tuberculosis infection in alveolar macrophages, but they have less impact on suppressing infection in MDM, which may be a bacterial niche. Importantly, CD4 T cell responses enhance MDM recruitment to the lung. Thus, the outcome of infection depends on the interaction between the T cell subset and the infected cell; both contribute to the resolution and persistence of the infection.

论文信息：

论文题目：Heterogeneity in lung macrophage control of Mycobacterium tuberculosis is modulated by T cells

期刊名称：Nature Communications

时间期卷：5, Article number: 5710 (2024)

在线时间：2024年7月8日

肺脏巨噬细胞圈门策略：

Alveolar macrophages (AM) were discriminated from other lung macrophages by their high levels of SiglecF and CD11c. CD11b expression divided AM into two subsets. Non-AM macrophages have been called recruited macrophages (RM), interstitial macrophages (IM) and CD11cHi monocyte-derived cells (MDC). We previously referred to these cells as CD11cHi; however, in recognition of heterogeneity in their CD11c expression, we have dropped the CD11c moniker. As these monocyte-derived cells are distinct from resident macrophages (e.g., AM), we refer to them as monocyte-derived macrophages (MDM). MDM were divided into three subsets based on their SiglecF and CD11c expression. The SiglecFintCD11c+ (MDM1) were the most variable between experiments and could be immature AM. SiglecF–CD11c+ (MDM2) were the most abundant of the three and were most like what we previously referred to as CD11cHi MDC (Fig. 2a). In additions, SiglecF-CD11c- (MDM3) may be nerve associated macrophages that have been recently described in the lung. Finally, we subdivided monocytes and DC (M/DC) based on CD11c, Ly6C, CD26, CD11b and MHCII expression (M/DC1-4). (Supplementary Fig. 1). The most abundant of these were M/DC1 (Ly6C–CD11cVARCD26+-CD11bvarMHCIIhi) and M/DC3 (Ly6C+CD11c–-CD26-CD11b+MHCIIlow). The former was likely a mixed DC population, and the latter were probably classical monocytes. M/DC2 (Ly6C+CD11c+CD26+CD11b+MHCIIhi) are likely a monocyte-derived DC population based on Ly6C expression.

参考意义：

我们在用荷兰liposoma品牌Clodronateliposomes清除肺脏巨噬细胞时，评价自己的清除体系，可以参照该文献的圈门策略。时刻记住，巨噬细胞的异质性，以及在模型发生和发展过程中的动态变化。参考文献时，即使一样的模型，由于采样时间点不同，巨噬细胞的清除，也有可能不太一致。