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

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.

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Mutation W222L at the Receptor Binding Site of Hemagglutinin Could Facilitate Viral Adaption from Equine Influenza A(H3N8) Virus to Dogs

Journal of Virology ◽

10.1128/jvi.01115-18 ◽

2018 ◽

Vol 92 (18) ◽

Cited By ~ 6

Author(s):

Feng Wen ◽

Sherry Blackmon ◽

Alicia K. Olivier ◽

Lei Li ◽

Minhui Guan ◽

...

Keyword(s):

Influenza A ◽

Molecular Mechanisms ◽

Animal Health ◽

Sialyl Lewis X ◽

Interspecies Transmission ◽

Glycosidic Linkage ◽

Influenza A Viruses ◽

Lewis X ◽

Sialyl Lewis ◽

H3n8 Virus

ABSTRACT An outbreak of respiratory disease caused by the equine-origin influenza A(H3N8) virus was first detected in dogs in 2004 and since then has been enzootic among dogs. Currently, the molecular mechanisms underlying host adaption of this virus from horses to dogs is unknown. Here, we have applied quantitative binding, growth kinetics, and immunofluorescence analyses to elucidate these mechanisms. Our findings suggest that a substitution of W222L in the hemagglutinin of the equine-origin A(H3N8) virus facilitated its host adaption to dogs. This mutation increased binding avidity of the virus specifically to receptor glycans with N-glycolylneuraminic acid (Neu5Gc) and sialyl Lewis X (SLeX) motifs. We have demonstrated these motifs are abundantly located in the submucosal glands of dog trachea. Our findings also suggest that in addition to the type of glycosidic linkage (e.g., α2,3-linkage or α2,6-linkage), the type of sialic acid (Neu5Gc or 5-N-acetyl neuraminic acid) and the glycan substructure (e.g., SLeX) also play an important role in host tropism of influenza A viruses. IMPORTANCE Influenza A viruses (IAVs) cause a significant burden on human and animal health, and mechanisms for interspecies transmission of IAVs are far from being understood. Findings from this study suggest that an equine-origin A(H3N8) IAV with mutation W222L at its hemagglutinin increased binding to canine-specific receptors with sialyl Lewis X and Neu5Gc motifs and, thereby, may have facilitated viral adaption from horses to dogs. These findings suggest that in addition to the glycosidic linkage (e.g., α2,3-linked and α2,6-linked), the substructure in the receptor saccharides (e.g., sialyl Lewis X and Neu5Gc) could present an interspecies transmission barrier for IAVs and drive viral mutations to overcome such barriers.

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Selectin glycoprotein ligands.

Acta Biochimica Polonica ◽

10.18388/abp.2000_4019 ◽

2000 ◽

Vol 47 (2) ◽

pp. 393-412 ◽

Cited By ~ 19

Author(s):

I Zak ◽

E Lewandowska ◽

W Gnyp

Keyword(s):

Biosynthetic Pathway ◽

Structure And Function ◽

Cell Interactions ◽

Sialyl Lewis X ◽

Lewis X ◽

Sialyl Lewis ◽

Selectin Ligands ◽

The Common ◽

And Function ◽

Lymphatic Organs

Lectin selectins and their counter-receptors participate in discontinuous cell-cell interactions concurrent with leukocyte tethering and rolling on endothelium, which, in consequence, leads to leukocyte penetration to lymphatic organs and generation of inflammation sites. Counter-receptors are glycoproteins in which carbohydrate units, the direct selectin ligands, are built into the polypeptide framework. In this review, the distribution, structure and function of the main ligands and counter-receptors for P-, L- and E-selectins known so far, have been discussed. The common biosynthetic pathway of sialyl-Lewis x and sulpho-sialyl-Lewis x determinants of selectin ligands has been described.

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