Listeria Adhesion Protein Induces Intestinal Epithelial Barrier Dysfunction for Bacterial Translocation

Drolia, Rishi; Tenguria, Shivendra; Durkes, Abigail C.; Turner, Jerrold R.; Bhunia, Arun K.

doi:10.1016/j.chom.2018.03.004

Cited by 148 publications

(191 citation statements)

References 53 publications

Supporting

Mentioning

172

Contrasting

Order By: Relevance

“…onto epithelial cells but also to activate NF-κΒ. NF-κΒ activation was shown to in turn upregulate TNF-α and IL-6, increasing epithelial permeability via cellular redistribution of host cell adhesion proteins 53 .…”

Section: Discussionmentioning

confidence: 99%

Mechanical competition triggered by innate immune signaling drives the collective extrusion of bacterially-infected epithelial cells

Bastounis

Alcade

Radhakrishnan

et al. 2020

Preprint

View full text Add to dashboard Cite

Intracellular bacterial pathogens often reprogram their mammalian host cells, including cell mechanical properties, to promote their own replication and spread. However, it is unclear whether mammalian host cells may modulate their biomechanics in response to infection in a way that would benefit the host by limiting bacterial infection. Inspired by this question, we monitored epithelial cell monolayers infected with low levels of Listeria monocytogenes. We found that, as the bacteria replicate and spread from cell to cell over several days, the infected host cells within the infection focus get progressively compressed by surrounding uninfected cells. Surrounding uninfected cells become highly polarized and move directionally towards the infection focus, squeezing the infected cells that eventually get extruded from the monolayer.Extruded cells continue adhering to the cellular monolayer, giving rise to a 3-dimensional (3D) mound of infected cells. We hypothesized that 3D mounding was driven by changes in the biomechanics of uninfected cells surrounding the mounds (surrounders) as well as the infected cells that eventually compose the mound (mounders). Indeed, we found that infected mounders, but not surrounders, become softer during infection and adhere more weakly on deformable matrices mimicking their natural environment. Through a combination of transcriptomics, pharmacological and genetic perturbations, we find that differentially upregulated innate immunity signaling, and downregulated cell-cell and cell-matrix adhesion pathways synergistically can drive the observed cellular competition between infected mounders and surrounders. Most importantly we find that activation of NF-κB is critical for mound formation, and show evidence that our findings extend to bacterial pathogens other than L. monocytogenes. Overall, our findings highlight the dynamic remodeling capability of epithelial tissue, and propose a novel biomechanical mechanism employed by host epithelial cells to eliminate bacterial infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanical competition triggered by innate immune signaling drives the collective extrusion of bacterially-infected epithelial cells

Bastounis

Alcade

Radhakrishnan

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…PCV2 infection did not increase the adhesion and invasion of SS2 to STEC during the experiment, suggesting that PCV2 promoted bacterial translocation across the epithelial barrier through the paracellular route, rather than the transcellular route. Although SS2 did not reduce protein levels of ZO-1 and occludin, the TJ were reorganized (data not published), which was reported to be associated with the increased paracellular permeability [38] and bacterial translocation [24].…”

Section: Discussionmentioning

confidence: 99%

“…The tissues were embedded in paraffin wax and cut into 5 μm thick sections. After the dewaxing process and antigen repairment as previously described [24], the slides were blocked with 2% BSA (Solarbio, Beijing, China). For Immunofluorescence staining of ZO-1 and occludin in STEC, the cells were fixed with 4% Paraformaldehyde (Biosharp Life Science, China) for 15 min before being blocked with 2% BSA for 1 h at 37 °C.…”

Section: Immunofluorescence Staining Of Zo-1 and Occludin Proteinsmentioning

confidence: 99%

Porcine circovirus type 2 exploits JNK-mediated disruption of tight junctions to facilitate Streptococcus suis translocation across the tracheal epithelium

Wang

Zhou

Lin

et al. 2020

Vet Res

View full text Add to dashboard Cite

Porcine circovirus type 2 (PCV2) is considered as the primary pathogen of porcine circovirus-associated disease (PCVAD), which results in significant economic losses worldwide. Clinically, PCV2 often causes disease through coinfection with other bacterial pathogens, including Streptococcus suis (S. suis), and especially the highly prevalent S. suis serotype 2 (SS2). The present study determined that continuous PCV2 infection in piglets down-regulates tight junction proteins (TJ) ZO-1 and occludin in the lungs. Swine tracheal epithelial cells (STEC) were used to explore the mechanisms and consequences of disruption of TJ, and an in vitro tracheal epithelial barrier model was established. Our results show that PCV2 infection in STEC decreases the expression levels of ZO-1 and occludin and increases the permeability of the tracheal epithelial barrier, resulting in easier translocation of SS2. Moreover, Western blot analysis indicates that PCV2 infection activates the JNK/MAPK pathway. The disruption of TJ in SETC and increased permeability of the epithelial barrier induced by PCV2 could be alleviated by inhibition of JNK phosphorylation, which indicates that the JNK/MAPK pathway regulates the expression of ZO-1 and occludin during PCV2 infection. This study allows us to better understand the mechanisms of PCV2 coinfection with bacterial pathogens and provides new insight into controlling the occurrence of PCVAD. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

show abstract

“…The majority of studies on L. monocytogenes infection have been conducted in animals 94 such as mice, and single cell line models such as colon adenocarcinoma cells or 95 macrophage cells [25,33] . Most knowledge of the innate and adaptive immune responses 96 has been learned from experimental L. monocytogenes infections of mice [34] .…”

mentioning

confidence: 99%

“…In the researches on the stage of intestinal infection, most analyzed virulence gene and survival 505 mechanism of L. monocytogenes, and the host response [50,51] . Furthermore, the 506 infection may alter host intestinal microbiota to promote bacterial colonization [25] . In 507 the proteomics analysis of L. monocytogenes, many studies focused on bacterial 508 proteins, and explored the relationship between some proteins and bacterial virulence 509 by comparing the different protein expression between different strains in stress, 510 biological metabolism, and virulence genes [23,39] .…”

mentioning

confidence: 99%

TMT-Based Quantitative Proteomic Analysis of Intestinal Organoids Infected byListeria monocytogeneswith Different Virulence

Haung

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

13Listeria monocytogenes (Lm) is an opportunistic food-borne pathogen that cause 14 listeriosis. L. monocytogenes belonged to different serovars presents with different 15 virulence in the host and caused different host reactions. To investigate the remodeling 16 of host proteome by differently toxic strains, the cellular protein responses of intestinal 17 organoids were analyzed using TMT labeling and high performance liquid 18 chromatography-mass spectrometry. Quantitative proteomic analysis revealed 6564 19 differentially expressed proteins, of which 5591 proteins were quantified. The fold-20 change cutoff was set at 1.3 (Lm vs control), the virulent strain caused 102 up-regulated 21 proteins and 52 down-regulated proteins, while the low virulent strain caused 188 up-22 regulated proteins and 25 down-regulated proteins. These identified proteins were 23 involved in the regulation of essential processes such as biological metabolism, energy 24 metabolism, and immune system process. Some selected proteins were screened by 25 Real-time PCR and Western blotting. These results revealed that differently toxic L. 26 monocytogenes induced similar biological functions and immune responses while had 27 different regulation on differential proteins in the pathway.28 Keywords: Listeria monocytogenes; virulence; proteomic; host response; intestinal 29 organoid.30to evade or modulate immune defences. For example, L. monocytogenes modified 87 bacterial ligands to avoid detection, modulated host signalling pathways to alter host 88 innate defences [32] . The detailed understanding of L. monocytogenes-host interactions 89 and infection and immunity is essential for elucidating these mechanisms. Therefore, 90 investigating the changes in the overall protein abundance of host cells by L. 91 monocytogenes can help to understand the relationship between the pathogenicity and 92 toxicity of the bacteria. 93The majority of studies on L. monocytogenes infection have been conducted in animals 94 such as mice, and single cell line models such as colon adenocarcinoma cells or 95 macrophage cells [25,33] . Most knowledge of the innate and adaptive immune responses 96 has been learned from experimental L. monocytogenes infections of mice [34] . In 97 addition to immune cells, intestinal epithelial cells were also involved in the defense 98 against L. monocytogenes infections. Studies explored that host responses caused by L. 99 monocytogenes included innate immune responses first activated by PRRs of intestinal 100 epithelial cells, immune cells recruited by downstream cytokines and adaptive immune 101 responses subsequently stimulated [32, 34] . However, a single immune model or intestinal 102 cell model both cannot completely reflect the damage of L. monocytogenes to the entire 103 intestinal epithelium. Recently, intestinal organoid was emerging as a more effective 104 infection model that reproduced the differentiation of intestinal epithelial cells, and 105showed the greatest similarity to the intestinal epithelium with respect to...

show abstract

Listeria Adhesion Protein Induces Intestinal Epithelial Barrier Dysfunction for Bacterial Translocation

Cited by 148 publications

References 53 publications

Mechanical competition triggered by innate immune signaling drives the collective extrusion of bacterially-infected epithelial cells

Mechanical competition triggered by innate immune signaling drives the collective extrusion of bacterially-infected epithelial cells

Porcine circovirus type 2 exploits JNK-mediated disruption of tight junctions to facilitate Streptococcus suis translocation across the tracheal epithelium

TMT-Based Quantitative Proteomic Analysis of Intestinal Organoids Infected byListeria monocytogeneswith Different Virulence

Contact Info

Product

Resources

About