scholarly journals Application of a gut-immune co-culture system for the study of N-glycan-dependent host-pathogen interactions of Campylobacter jejuni

2019 ◽  
Author(s):  
Cristina Y. Zamora ◽  
Elizabeth M. Ward ◽  
Jemila C. Kester ◽  
Wen Li Kelly Chen ◽  
Jason G. Velazquez ◽  
...  
Keyword(s):  
Immune System ◽  
Campylobacter Jejuni ◽  
Outer Membrane Vesicles ◽  
Protein Glycosylation ◽  
Bacterial Invasion ◽  
Host Pathogen Interactions ◽  
Barrier Functions ◽  
Immune System Activation ◽  
Culture Model ◽  
Host Pathogen

AbstractAn in vitro gut-immune co-culture model with apical and basal accessibility, designed to more closely resemble a human intestinal microenvironment, was employed to study the role of the Nlinked protein glycosylation (Pgl) pathway in Campylobacter jejuni pathogenicity. The gutimmune co-culture (GIC) was developed to model important aspects of the human small intestine by the inclusion of mucin producing goblet cells, human enterocytes, and dendritic cells, bringing together a mucus-containing epithelial monolayer with elements of the innate immune system. The utility of the system was demonstrated by characterizing host-pathogen interactions facilitated by N-linked glycosylation, such as host epithelial barrier functions, bacterial invasion and immunogenicity. Changes in human intestinal barrier functions in the presence of 11168 C. jejuni (wildtype) strains were quantified using GICs. The glycosylationdeficient strain 11168 ΔpglE was 100-fold less capable of adhering to and invading this intestinal model in cell infectivity assays. Quantification of inflammatory signaling revealed that 11168ΔpglE differentially modulated inflammatory responses in different intestinal microenvironments, suppressive in some but activating in others. Virulence-associated outer membrane vesicles produced by wildtype and 11168ΔpglE C. jejuni were shown to have differential composition and function, with both leading to immune system activation when provided to the gut-immune co-culture model. This analysis of aspects of C. jejuni infectivity in the presence and absence of its N-linked glycome, is enabled by application of the gut-immune model and we anticipate that this system will be applicable to further studies of C. jejuni and other enteropathogens of interest.

scholarly journals Application of a gut-immune co-culture system for the study of N-glycan-dependent host–pathogen interactions of Campylobacter jejuni

Glycobiology ◽  
2020 ◽  
Vol 30 (6) ◽  
pp. 374-381 ◽  
Author(s):  
Cristina Y Zamora ◽  
Elizabeth M Ward ◽  
Jemila C Kester ◽  
Wen Li Kelly Chen ◽  
Jason G Velazquez ◽  
...  
Keyword(s):  
Immune System ◽  
Campylobacter Jejuni ◽  
Outer Membrane Vesicles ◽  
Protein Glycosylation ◽  
Bacterial Invasion ◽  
Host Pathogen Interactions ◽  
Barrier Functions ◽  
Immune System Activation ◽  
Culture Model ◽  
Host Pathogen

Abstract An in vitro gut-immune co-culture model with apical and basal accessibility, designed to more closely resemble a human intestinal microenvironment, was employed to study the role of the N-linked protein glycosylation pathway in Campylobacter jejuni pathogenicity. The gut-immune co-culture (GIC) was developed to model important aspects of the human small intestine by the inclusion of mucin-producing goblet cells, human enterocytes and dendritic cells, bringing together a mucus-containing epithelial monolayer with elements of the innate immune system. The utility of the system was demonstrated by characterizing host–pathogen interactions facilitated by N-linked glycosylation, such as host epithelial barrier functions, bacterial invasion and immunogenicity. Changes in human intestinal barrier functions in the presence of 11168 C. jejuni (wildtype) strains were quantified using GICs. The glycosylation-impaired strain 11168 ΔpglE was 100-fold less capable of adhering to and invading this intestinal model in cell infectivity assays. Quantification of inflammatory signaling revealed that 11168ΔpglE differentially modulated inflammatory responses in different intestinal microenvironments, suppressive in some but activating in others. Virulence-associated outer membrane vesicles produced by wildtype and 11168ΔpglE C. jejuni were shown to have differential composition and function, with both leading to immune system activation when provided to the gut-immune co-culture model. This analysis of aspects of C. jejuni infectivity in the presence and absence of its N-linked glycome is enabled by application of the gut-immune model, and we anticipate that this system will be applicable to further studies of C. jejuni and other enteropathogens of interest.

scholarly journals RNA-Sequencing Analyses of Small Bacterial RNAs and their Emergence as Virulence Factors in Host-Pathogen Interactions

2020 ◽  
Vol 21 (5) ◽  
pp. 1627 ◽  
Author(s):  
Idrissa Diallo ◽  
Patrick Provost
Keyword(s):  
Rna Sequencing ◽  
Virulence Factors ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Rna Seq ◽  
Host Pathogen Interactions ◽  
Bioinformatics Analyses ◽  
Additional Layer ◽  
Host Pathogen

Proteins have long been considered to be the most prominent factors regulating so-called invasive genes involved in host-pathogen interactions. The possible role of small non-coding RNAs (sRNAs), either intracellular, secreted or packaged in outer membrane vesicles (OMVs), remained unclear until recently. The advent of high-throughput RNA-sequencing (RNA-seq) techniques has accelerated sRNA discovery. RNA-seq radically changed the paradigm on bacterial virulence and pathogenicity to the point that sRNAs are emerging as an important, distinct class of virulence factors in both gram-positive and gram-negative bacteria. The potential of OMVs, as protectors and carriers of these functional, gene regulatory sRNAs between cells, has also provided an additional layer of complexity to the dynamic host-pathogen relationship. Using a non-exhaustive approach and through examples, this review aims to discuss the involvement of sRNAs, either free or loaded in OMVs, in the mechanisms of virulence and pathogenicity during bacterial infection. We provide a brief overview of sRNA origin and importance and describe the classical and more recent methods of identification that have enabled their discovery, with an emphasis on the theoretical lower limit of RNA sizes considered for RNA sequencing and bioinformatics analyses.

A Primary Human Macrophage-Enteroid Co-Culture Model to Investigate Mucosal Gut Physiology and Host-Pathogen Interactions

2017 ◽  
Vol 152 (5) ◽  
pp. S56-S57
Author(s):  
Nicholas W. Baetz ◽  
Gaelle Noel ◽  
Janet Staab ◽  
Mark Donowitz ◽  
Olga Kovbasnjuk ◽  
...  
Keyword(s):  
Human Macrophage ◽  
Primary Human Macrophage ◽  
Host Pathogen Interactions ◽  
Culture Model ◽  
Host Pathogen ◽  
Gut Physiology

Alterations in glycosylation as biomarkers for cancer detection

2010 ◽  
Vol 63 (4) ◽  
pp. 322-329 ◽  
Author(s):  
Celso A Reis ◽  
Hugo Osorio ◽  
Luisa Silva ◽  
Catarina Gomes ◽  
Leonor David
Keyword(s):  
Cell Differentiation ◽  
Cancer Detection ◽  
Human Cancer ◽  
Protein Glycosylation ◽  
Cell Trafficking ◽  
Tumour Invasion ◽  
Host Pathogen Interactions ◽  
Pathological Conditions ◽  
Major Class ◽  
Host Pathogen

Glycoconjugates constitute a major class of biomolecules which include glycoproteins, glycosphingolipids and proteoglycans. Glycans are involved in several physiological and pathological conditions, such as host–pathogen interactions, cell differentiation, migration, tumour invasion and metastisation, cell trafficking and signalling. Cancer is associated with glycosylation alterations in glycoproteins and glycolipids. This review describes various aspects of protein glycosylation with the focus on alterations associated with human cancer. The application of these glycosylation modifications as biomarkers for cancer detection in tumour tissues and serological assays is summarised.

scholarly journals Genetic background of IL-10−/− mice alters host–pathogen interactions with Campylobacter jejuni and influences disease phenotype

2008 ◽  
Vol 45 (4) ◽  
pp. 241-257 ◽  
Author(s):  
L.S. Mansfield ◽  
J.S. Patterson ◽  
B.R. Fierro ◽  
A.J. Murphy ◽  
V.A. Rathinam ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Genetic Background ◽  
Disease Phenotype ◽  
Host Pathogen Interactions ◽  
Host Pathogen

scholarly journals Role of Protein Glycosylation in Host-Pathogen Interaction

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1022 ◽  
Author(s):  
Borong Lin ◽  
Xue Qing ◽  
Jinling Liao ◽  
Kan Zhuo
Keyword(s):  
Interaction Mechanism ◽  
Protein Glycosylation ◽  
Post Translational Modification ◽  
Host Pathogen Interactions ◽  
Pathogen Virulence ◽  
Host Pathogen Interaction ◽  
Bacterial Adhesins ◽  
Host Pathogen ◽  
Induce Resistance ◽  
Regulate Protein

Host-pathogen interactions are fundamental to our understanding of infectious diseases. Protein glycosylation is one kind of common post-translational modification, forming glycoproteins and modulating numerous important biological processes. It also occurs in host-pathogen interaction, affecting host resistance or pathogen virulence often because glycans regulate protein conformation, activity, and stability, etc. This review summarizes various roles of different glycoproteins during the interaction, which include: host glycoproteins prevent pathogens as barriers; pathogen glycoproteins promote pathogens to attack host proteins as weapons; pathogens glycosylate proteins of the host to enhance virulence; and hosts sense pathogen glycoproteins to induce resistance. In addition, this review also intends to summarize the roles of lectin (a class of protein entangled with glycoprotein) in host-pathogen interactions, including bacterial adhesins, viral lectins or host lectins. Although these studies show the importance of protein glycosylation in host-pathogen interaction, much remains to be discovered about the interaction mechanism.

scholarly journals A novel 3D culture model of fungal keratitis to explore host-pathogen interactions within the stromal environment

2021 ◽  
Vol 207 ◽  
pp. 108581
Author(s):  
Marina E. Brown ◽  
Micaela L. Montgomery ◽  
Manali M. Kamath ◽  
Sarah Nicholas ◽  
Yutao Liu ◽  
...  
Keyword(s):  
3D Culture ◽  
Fungal Keratitis ◽  
Host Pathogen Interactions ◽  
Culture Model ◽  
Host Pathogen ◽  
3D Culture Model

scholarly journals When the Going Gets Rough: The Significance of Brucella Lipopolysaccharide Phenotype in Host–Pathogen Interactions

2021 ◽  
Vol 12 ◽  
Author(s):  
Lauren W. Stranahan ◽  
Angela M. Arenas-Gamboa
Keyword(s):  
Immune System ◽  
Outer Membrane ◽  
Vaccine Development ◽  
Outer Membrane Proteins ◽  
Host Cells ◽  
Host Immune System ◽  
Host Pathogen Interactions ◽  
Zoonotic Infections ◽  
Host Pathogen

Brucella is a facultatively intracellular bacterial pathogen and the cause of worldwide zoonotic infections, infamous for its ability to evade the immune system and persist chronically within host cells. Despite the frequent association with attenuation in other Gram-negative bacteria, a rough lipopolysaccharide phenotype is retained by Brucella canis and Brucella ovis, which remain fully virulent in their natural canine and ovine hosts, respectively. While these natural rough strains lack the O-polysaccharide they, like their smooth counterparts, are able to evade and manipulate the host immune system by exhibiting low endotoxic activity, resisting destruction by complement and antimicrobial peptides, entering and trafficking within host cells along a similar pathway, and interfering with MHC-II antigen presentation. B. canis and B. ovis appear to have compensated for their roughness by alterations to their outer membrane, especially in regards to outer membrane proteins. B. canis, in particular, also shows evidence of being less proinflammatory in vivo, suggesting that the rough phenotype may be associated with an enhanced level of stealth that could allow these pathogens to persist for longer periods of time undetected. Nevertheless, much additional work is required to understand the correlates of immune protection against the natural rough Brucella spp., a critical step toward development of much-needed vaccines. This review will highlight the significance of rough lipopolysaccharide in the context of both natural disease and host–pathogen interactions with an emphasis on natural rough Brucella spp. and the implications for vaccine development.

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