Mycobacterium tuberculosis Infection Up-Regulates Sialyl Lewis X Expression in the Lung Epithelium.

Rita Matos,Pedro N S Rodrigues,Stefan Mereiter,Margarida Saraiva,Ana Magalhães,Kaori L Fonseca,Fátima Gartner,Joana Gomes,Ana Raquel Maceiras,Celso A Reis,Cristina Vilaplana

doi:10.3390/microorganisms9010099

Abstract

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 Mycobacterium tuberculosis. We have recently reported that perturbing the core-2 O-glycans biosynthetic pathway increases the host susceptibility to M. tuberculosis 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 M. tuberculosis 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 O-glycans biosynthetic pathway. This study provides novel insights into previously unappreciated molecular mechanisms involving glycosylation, which modulate the host response to M. tuberculosis infection, possibly contributing to shape TB disease outcome.

Highlights

IntroductionGlycosylation is a common post-translation modification, recognized to regulate several key biological processes, either on homeostasis or pathological conditions [1,2,3]
Introduction censeeMDPI, Basel, Switzerland.Glycosylation is a common post-translation modification, recognized to regulate several key biological processes, either on homeostasis or pathological conditions [1,2,3].This highly regulated enzyme-mediated modification occurs mainly on the Golgi apparatus and results in the production of glycosidic linkages of saccharides to other saccharides, proteins or lipids [4]
In the case of H. pylori, we showed that infection results in increased expression of sialylated Lewis antigens in the gastric epithelium, which are recognized by the bacterial sialic acid binding adhesin (SabA), contributing to a close contact with the gastric mucosal cells and a tighter fit of the infection load with proficient transfer of virulence factors [12,13]

Summary

Introduction

Glycosylation is a common post-translation modification, recognized to regulate several key biological processes, either on homeostasis or pathological conditions [1,2,3]. This highly regulated enzyme-mediated modification occurs mainly on the Golgi apparatus and results in the production of glycosidic linkages of saccharides to other saccharides, proteins or lipids [4]. Glycans and glycoconjugates can be classified into several classes, including the protein linked N-glycans and O-glycans.

Methods

Results

Conclusion