b8bce0225767dccf60eb2235ad7cb44c pmc_33406734.pdf 3894219a3d284d0712ccc39fb7ae2b0e41e7ca29 pmc_33406734.pdf f31290483d56fb9e2f974c7171c68edb60eb55f202bef064bc9f4dcd4cb27b6f pmc_33406734.pdf Title: Mycobacterium tuberculosis Infection Up-Regulates Sialyl Lewis X Expression in the Lung Epithelium Subject: 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. Keywords: Mycobacterium tuberculosis; lung glycophenotype; Lewis antigens; Sialyl-Lewis X Author: Rita Matos, Kaori L. Fonseca, Stefan Mereiter, Ana Raquel Maceiras, Joana Gomes, Cristina Vilaplana, Fátima Gartner, Pedro N. S. Rodrigues, Celso A. Reis, Margarida Saraiva and Ana Magalhães Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Tue Jan 5 09:03:59 2021 CET ModDate: Tue Jan 5 09:24:29 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2721220 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XKJBXI+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 COSIXW+VnURWPalladioL Type 1 Custom yes yes no 15 0 AOTGTK+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 VSDRPX+URWPalladioL-BoldItal Type 1 Custom yes yes no 24 0 AGWBZC+URWPalladioL-Bold Type 1 Custom yes yes no 28 0 JJUPHE+URWPalladioL-Roma Type 1 Custom yes yes no 32 0 SIXRFS+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 40 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 62 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 66 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 70 0 VVSYYB+EURM10 Type 1 Builtin yes yes no 82 0 QGYIMR+CMSY10 Type 1 Builtin yes yes no 89 0 IMPNHP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 109 0 IMPNIB+PalatinoLinotype TrueType WinAnsi yes yes no 112 0 IMPNID+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 115 0 IMPNHP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 135 0 IMPNIA+PalatinoLinotype CID TrueType Identity-H yes yes yes 138 0 IMPNIB+PalatinoLinotype TrueType WinAnsi yes yes no 144 0 IMPNID+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 147 0 IMPNHP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 170 0 IMPNIA+PalatinoLinotype CID TrueType Identity-H yes yes yes 173 0 IMPNIB+PalatinoLinotype TrueType WinAnsi yes yes no 179 0 IMPNID+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 182 0 IMPNHP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 199 0 IMPNIA+PalatinoLinotype CID TrueType Identity-H yes yes yes 202 0 IMPNIB+PalatinoLinotype TrueType WinAnsi yes yes no 208 0 IMPNID+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 211 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2021-09-11 03:55:04 CEST RepresentationInformation: pmc_33406734.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-02-01 03:47:50 CET Size: 2721220 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 431 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Ethics Statement Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Bacteria and Bacterial Growth Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: M. tuberculosis Infection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Tissue Samples and Immunohistochemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: RNA Extraction, cDNA Synthesis and Real-Time PCR Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Children: Item: Title: M. tuberculosis Infected Lungs Display Increased Sialylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: M. tuberculosis Infection Up-Regulates the Transcription of Enzymes Controlling the Biosynthesis of SLeX on Core-2 O-Glycans Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Lack of Gcnt1 Does not Preclude Increased Lung Sialylation upon M. tuberculosis Infection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Info: Title: Mycobacterium tuberculosis Infection Up-Regulates Sialyl Lewis X Expression in the Lung Epithelium Author: Rita Matos, Kaori L. Fonseca, Stefan Mereiter, Ana Raquel Maceiras, Joana Gomes, Cristina Vilaplana, Fátima Gartner, Pedro N. S. Rodrigues, Celso A. Reis, Margarida Saraiva and Ana Magalhães Subject: 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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