Matos Rita, Fonseca Kaori L, Mereiter Stefan, Maceiras Ana Raquel, Gomes Joana, Vilaplana Cristina, Gartner Fátima, Rodrigues Pedro N S, Reis Celso A, Saraiva Margarida, Magalhães Ana
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal.
Microorganisms. 2021 Jan 4;9(1):99. doi: 10.3390/microorganisms9010099.
Glycans display increasingly recognized roles in pathological contexts, however, their impact in the host-pathogen interplay in many infectious diseases remains largely unknown. This is the case for tuberculosis (TB), one of the ten most fatal diseases worldwide, caused by infection of the bacteria . We have recently reported that perturbing the core-2 -glycans biosynthetic pathway increases the host susceptibility to infection, by disrupting the neutrophil homeostasis and enhancing lung pathology. In the present study, we show an increased expression of the sialylated glycan structure Sialyl-Lewis X (SLeX) in the lung epithelium upon infection. This increase in SLeX glycan epitope is accompanied by an altered lung tissue transcriptomic signature, with up-regulation of genes codifying enzymes that are involved in the SLeX core-2 -glycans biosynthetic pathway. This study provides novel insights into previously unappreciated molecular mechanisms involving glycosylation, which modulate the host response to infection, possibly contributing to shape TB disease outcome.
聚糖在病理环境中的作用日益受到认可，然而，它们在许多传染病的宿主-病原体相互作用中的影响仍 largely 未知。结核病（TB）就是这种情况，它是全球十大最致命疾病之一，由细菌感染引起。我们最近报告称，干扰核心 2 -聚糖生物合成途径会破坏中性粒细胞稳态并加剧肺部病理，从而增加宿主对感染的易感性。在本研究中，我们发现感染后肺上皮中唾液酸化聚糖结构唾液酸化路易斯 X（SLeX）的表达增加。SLeX 聚糖表位的这种增加伴随着肺组织转录组特征的改变，参与 SLeX 核心 2 -聚糖生物合成途径的编码酶的基因上调。本研究为涉及糖基化的先前未被认识的分子机制提供了新见解，这些机制调节宿主对感染的反应，可能有助于塑造结核病的疾病结局。
