中性粒细胞在结核病 (TB) 期间可能有益，也可能有害。基于 MHC-II 和程序性死亡配体 1 (PD-L1) 的表达，我们区分了感染分枝杆菌的小鼠肺部中两种功能和转录不同的中性粒细胞亚群。炎症性 [MHC-II-、PD-L1lo] 中性粒细胞响应剧毒分枝杆菌，在肺部产生炎症小体依赖性 IL-1β，并“加速”有害炎症，这种情况在 IFN-γR-/- 小鼠中高度加剧。调节性 [MHC-II、PD-L1hi] 中性粒细胞通过抑制 T 细胞增殖和 IFN-γ 产生来“抑制”炎症。这种有益的调节依赖于 PD-L1，并由中性粒细胞中的 IFN-γR 信号传导控制。来自北京基因型的高毒力 HN878 菌株通过调节性中性粒细胞抑制 PD-L1 表达，消除制动功能并引发肺部有害的过度炎症。这些发现为中性粒细胞在结核病中发挥的作用增添了一层复杂性，并可能解释在接受抗 PD-L1 治疗的癌症患者中观察到的这种疾病的重新激活。© 2024 Doz-Deblauwe 等人。

Neutrophils can be beneficial or deleterious during tuberculosis (TB). Based on the expression of MHC-II and programmed death ligand 1 (PD-L1), we distinguished two functionally and transcriptionally distinct neutrophil subsets in the lungs of mice infected with mycobacteria. Inflammatory [MHC-II-, PD-L1lo] neutrophils produced inflammasome-dependent IL-1β in the lungs in response to virulent mycobacteria and "accelerated" deleterious inflammation, which was highly exacerbated in IFN-γR-/- mice. Regulatory [MHC-II+, PD-L1hi] neutrophils "brake" inflammation by suppressing T-cell proliferation and IFN-γ production. Such beneficial regulation, which depends on PD-L1, is controlled by IFN-γR signaling in neutrophils. The hypervirulent HN878 strain from the Beijing genotype curbed PD-L1 expression by regulatory neutrophils, abolishing the braking function and driving deleterious hyperinflammation in the lungs. These findings add a layer of complexity to the roles played by neutrophils in TB and may explain the reactivation of this disease observed in cancer patients treated with anti-PD-L1.© 2024 Doz-Deblauwe et al.