Modulation of immunity and disease by glycans is increasingly recognized. However, how host glycosylation shapes and is shaped by tuberculosis remains poorly understood. We show that deficiency in the glucosaminyl (N-acetyl) transferase 1 (Gcnt1), a key enzyme for core-2 O-glycans biosynthesis, drives susceptibility to Mycobacterium tuberculosis infection. The increased susceptibility of Gcnt1 deficient mice was characterized by extensive lung immune pathology, mechanistically related to neutrophils. Uninfected Gcnt1 deficient mice presented bone marrow, blood and lung neutrophilia, which further increased with infection. Blood neutrophilia required Gcnt1 deficiency in the hematopoietic compartment, relating with enhanced granulopoiesis, but normal cellular egress from the bone marrow. Interestingly, for the blood neutrophilia to translate into susceptibility to M. tuberculosis infection, Gnct1 deficiency in the stroma was also necessary. Complete Gcnt1 deficiency associated with increased lung expression of the neutrophil chemoattractant CXCL2. Lastly, we demonstrate that the transcript levels of various glycosyltransferase-encoding genes were altered in whole blood of active tuberculosis patients and that sialyl Lewis x, a glycan widely present in human neutrophils, was detected in the lung of tuberculosis patients. Our findings reveal a previously unappreciated link between Gcnt1, neutrophilia and susceptibility to M. tuberculosis infection, uncovering new players balancing the immune response in tuberculosis.

聚糖对免疫和疾病的调节作用越来越受到人们的认可。然而，宿主糖基化如何塑造以及如何被结核病塑造仍然知之甚少。我们表明，核心 2 O-聚糖生物合成的关键酶 - 氨基葡萄糖（N-乙酰基）转移酶 1 (Gcnt1) 的缺乏会导致结核分枝杆菌感染的易感性。Gcnt1缺陷小鼠的易感性增加的特点是广泛的肺免疫病理学，在机制上与中性粒细胞有关。未感染的 Gcnt1缺陷小鼠出现骨髓、血液和肺中性粒细胞增多，并随着感染进一步增加。血液中性粒细胞增多需要造血隔室中的 Gcnt1 缺陷，与增强的粒细胞生成有关，但正常的细胞从骨髓流出。有趣的是，血液中性粒细胞增多转化为对结核分枝杆菌的易感性感染，基质中的 Gnct1 缺陷也是必要的。Gcnt1 完全缺乏与中性粒细胞趋化因子 CXCL2 的肺表达增加有关。最后，我们证明了各种糖基转移酶编码基因的转录水平在活动性结核病患者的全血中发生了改变，并且在结核病患者的肺中检测到了唾液酸 Lewis x（一种广泛存在于人类嗜中性粒细胞中的聚糖）。我们的研究结果揭示了 Gcnt1、中性粒细胞增多和结核分枝杆菌感染易感性之间以前未被重视的联系，揭示了平衡结核病免疫反应的新参与者。