Departamento de Química Biológica. Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina.
Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Autophagy. 2021 Sep;17(9):2629-2638. doi: 10.1080/15548627.2020.1825273. Epub 2020 Oct 4.
Neutrophils infected with () predominate in tuberculosis patients' lungs. Neutrophils phagocytose the pathogen, but the mechanism of pathogen elimination is controversial. Macroautophagy/autophagy, a crucial mechanism for several neutrophil functions, can be modulated by immunological mediators. The costimulatory molecule SLAMF1 can act as a microbial sensor in macrophages being also able to interact with autophagy-related proteins. Here, we demonstrate for the first time that human neutrophils express SLAMF1 upon -stimulation. Furthermore, SLAMF1 was found colocalizing with LC3B vesicles, and activation of SLAMF1 increased neutrophil autophagy induced by . Finally, tuberculosis patients' neutrophils displayed reduced levels of SLAMF1 and lower levels of autophagy against as compared to healthy controls. Altogether, these results indicate that SLAMF1 participates in neutrophil autophagy during active tuberculosis. AFB: acid-fast bacilli; BafA1: bafilomycin A; CLL: chronic lymphocytic leukemia; DPI: diphenyleneiodonium; EVs: extracellular vesicles; FBS: fetal bovine serum; HD: healthy donors; HR: high responder (tuberculosis patient); IFNG: interferon gamma; IL1B: interleukin 1 beta; IL17A: interleukin 17A; IL8: interleukin 8; LR: low responder (tuberculosis patient); mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MAPK1/ERK2: mitogen-activated protein kinase 1; MAPK14/p38: mitogen-activated protein kinase 14; tuberculosis; Ag: , Strain H37Rv, whole cell lysate; NETs: neutrophils extracellular traps; PPD: purified protein derivative; ROS: reactive oxygen species; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; SLAMF1: signaling lymphocytic activation molecule family member 1; TB: tuberculosis; TLR: toll like receptor.
受感染的（）中性粒细胞在肺结核患者肺部中占优势。中性粒细胞吞噬病原体，但病原体清除的机制仍存在争议。巨自噬/自噬是几种中性粒细胞功能的关键机制，可被免疫调节剂调节。共刺激分子 SLAMF1 可作为巨噬细胞中的微生物传感器，也能够与自噬相关蛋白相互作用。在这里，我们首次证明 -刺激可诱导人中性粒细胞表达 SLAMF1。此外，发现 SLAMF1 与 LC3B 囊泡共定位，并且 SLAMF1 的激活增加了由诱导的中性粒细胞自噬。最后，与健康对照相比，肺结核患者的中性粒细胞显示出 SLAMF1 水平降低和针对的自噬水平降低。总的来说，这些结果表明 SLAMF1 参与了活动性肺结核中的中性粒细胞自噬。AFB：抗酸杆菌；BafA1：巴弗霉素 A；CLL：慢性淋巴细胞白血病；DPI：二苯基碘；EVs：细胞外囊泡；FBS：胎牛血清；HD：健康供体；HR：高反应者（肺结核患者）；IFNG：干扰素 γ；IL1B：白细胞介素 1β；IL17A：白细胞介素 17A；IL8：白细胞介素 8；LR：低反应者（肺结核患者）；mAb：单克隆抗体；MAP1LC3/LC3：微管相关蛋白 1 轻链 3；MAPK：丝裂原活化蛋白激酶；MAPK1/ERK2：丝裂原活化蛋白激酶 1；MAPK14/p38：丝裂原活化蛋白激酶 14；结核分枝杆菌；Ag：，H37Rv 株，全细胞裂解物；NETs：中性粒细胞细胞外陷阱；PPD：纯化蛋白衍生物；ROS：活性氧；PIK3C3/VPS34：磷脂酰肌醇 3-激酶催化亚单位 3；SLAMF1：信号淋巴细胞激活分子家族成员 1；TB：结核；TLR： toll 样受体。
