The interaction of macrophages and CD8 T cells in bronchoalveolar lavage fluid is associated with latent tuberculosis infection

Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune responses. However, the immune mechanisms that govern the progression from LTBI to TB remain poorly defined in humans. Here, we profiled the lung immune cell populations within the bronchoalveolar lavage fluid (BALF) from patients with LTBI or TB using single-cell RNA sequencing (scRNA-seq). We found that Mtb infection substantially changed the immune cell compartments in the BALF, especially for the three subsets of macrophages, monocyte macrophage (MM)-CCL23, MM-FCN1, and MM-SPP1, which were found to be associated with the disease status of TB infection. Notably, MM-CCL23 cells derived from monocytes after stimulation with Mtb were characterized by high levels of chemokine (<i>CCL23</i> and <i>CXCL5</i>) production and might serve as a marker for Mtb infection. The MM-CCL23 population mainly recruited CD8-CCR6 T cells through CCL20/CCR6, which was a prominent feature associated with protection immunity in LTBI. This study improves our understanding of the lung immune landscape during Mtb infection, which may inform future vaccine design for protective immunity.

结核分枝杆菌（Mycobacterium tuberculosis, Mtb）感染，包括活动性肺结核（active tuberculosis, TB）与潜伏性结核分枝杆菌感染（latent Mtb infection, LTBI），会因宿主免疫应答的差异而引发多样的疾病转归。然而，调控从潜伏性结核感染进展为活动性肺结核的免疫机制在人类中仍未被充分阐明。本研究通过单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术，对潜伏性结核感染或活动性肺结核患者的支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中的肺部免疫细胞群进行了分析。研究发现，结核分枝杆菌感染显著改变了支气管肺泡灌洗液中的免疫细胞组成，尤其是三类巨噬细胞亚群：单核细胞来源巨噬细胞（monocyte macrophage, MM）-CCL23、MM-FCN1及MM-SPP1，上述亚群均与结核分枝杆菌感染的疾病状态密切相关。值得注意的是，经结核分枝杆菌刺激后由单核细胞分化而来的MM-CCL23细胞，以高表达趋化因子CCL23与CXCL5为特征，或可作为结核分枝杆菌感染的潜在标志物。MM-CCL23细胞群主要通过CCL20/CCR6轴招募CD8-CCR6 T细胞，这一特征是与潜伏性结核感染中保护性免疫相关的显著标志。本研究加深了我们对结核分枝杆菌感染过程中肺部免疫微环境的认知，或可为未来基于保护性免疫的疫苗研发提供理论参考。