Nature Communications： T細(xì)胞調(diào)節(jié)結(jié)核分枝桿菌感染肺巨噬細(xì)胞控制的異質(zhì)性

中文摘要：

結(jié)核分枝桿菌感染后，肺泡巨噬細(xì)胞最初被感染，但無效地限制了細(xì)菌復(fù)制。當(dāng)主要的感染細(xì)胞生態(tài)位從肺泡轉(zhuǎn)向單核細(xì)胞衍生的巨噬細(xì)胞 （MDM） 時，結(jié)核分枝桿菌在肺中不同細(xì)胞類型中的分布隨著 T 細(xì)胞免疫的開始而變化。我們假設(shè)不同細(xì)胞類型之間細(xì)菌分布的變化是由感染細(xì)胞的 T 細(xì)胞識別差異及其隨后激活的抗菌效應(yīng)機(jī)制驅(qū)動的。我們發(fā)現(xiàn) CD4 和 CD8 T 細(xì)胞可有效消除肺泡巨噬細(xì)胞中的結(jié)核分枝桿菌感染，但它們對抑制 MDM 感染的影響較小，MDM 可能是一個細(xì)菌生態(tài)位。重要的是，CD4 T 細(xì)胞反應(yīng)增強(qiáng)了 MDM 向肺部的募集。因此，感染的結(jié)果取決于 T 細(xì)胞亞群和感染細(xì)胞之間的相互作用;兩者都有助于感染的消退和持續(xù)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.

論文信息：

論文題目：Heterogeneity in lung macrophage control of Mycobacterium tuberculosis is modulated by T cells

期刊名稱：Nature Communications

時間期卷：5, Article number: 5710 (2024)

在線時間：2024年7月8日

肺臟巨噬細(xì)胞圈門策略：

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.

參考意義：

我們在用荷蘭liposoma品牌Clodronateliposomes清除肺臟巨噬細(xì)胞時，評價自己的清除體系，可以參照該文獻(xiàn)的圈門策略。時刻記住，巨噬細(xì)胞的異質(zhì)性，以及在模型發(fā)生和發(fā)展過程中的動態(tài)變化。參考文獻(xiàn)時，即使一樣的模型，由于采樣時間點(diǎn)不同，巨噬細(xì)胞的清除，也有可能不太一致。