Mucus blocks probiotics but increases penetration of motile pathogens and induces TNF‐α and IL‐8 secretion

Sharma, Abhinav; Raman, Vishnu; Lee, Jungwoo; Forbes, Neil S.

doi:10.1002/bit.27383

Cited by 5 publications

(22 citation statements)

References 59 publications

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“…Moreover, the mucus is also the first barrier protecting the gut from being invaded by the bacteria. Mucus is critical for the intestinal health since disruption of this boundary will probably result in bacterial penetration of mucus barrier and induce intestinal inflammation (Liu et al, 2020;Sharma et al, 2020;Son et al, 2020). It has been reported that gut bacteria could colonize the intestinal mucus layer in vivo and adhere to HT-29 cell in vitro (Altamimi et al, 2016;Engevik et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells

Lu²,

Mao

et al. 2021

Front. Cell. Infect. Microbiol.

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C. butyricum is a common gut commensal bacterium, which has many positive functions in human intestine. In this study, we investigated the effects of monosaccharide and its derivatives on the adhesion of C. butyricum to the mucus of HT-29 cells. RNA interference was performed to assess the roles of MUC2 and glycan in the adhesion of C. butyricum to HT-29 cells. The effects of C. butyricum on the glycosylation of mucins were assayed with fluorescence microscope. The expression levels of mucins and glycotransferases were also determined. The results showed that C. butyricum could adhere to the mucins secreted by HT-29 cells. Several kinds of monosaccharides inhibited the adhesion of C. butyricum to HT-29 cells, which suggested that the mucus glycan was the attaching sites of this bacterium. Knockdown of MUC2, FUT2 or GALNT7 significantly decreased the numbers of the bacteria adhering to HT-29 cells. When colonizing on the surface of HT-29 cells, C. butyricum could increase the production of mucins, promote the expression of glycotransferase, and induce the glycosylation of mucins. These results demonstrated that the glycan of mucus played important roles in the adhesion of C. butyricum to HT-29 cells. This study indicates for the first time that C. butyricum possesses the ability to modulate the glycosylation profile of mucus secreted by HT-29 cells. These findings contribute to understanding the mechanism of interaction between colonic epithelial cells and commensal bacteria.

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Section: Introductionmentioning

confidence: 99%

Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells

Lu²,

Mao

et al. 2021

Front. Cell. Infect. Microbiol.

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“…The barrier effect of the intestinal mucus layer to bacteria penetration has also been investigated for other bacterial strains. Sharma and co-workers showed that non-motile probiotic bacteria were significantly entrapped in a mucus gel layer whereas the penetration of the flagellated Salmonella pathogen after 12 h infection was even enhanced when the mucus layer was present in the model [ 62 ]. These results differ from the ones obtained by Kim et al [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Mimicking the Intestinal Host–Pathogen Interactions in a 3D In Vitro Model: The Role of the Mucus Layer

et al. 2022

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The intestinal mucus lines the luminal surface of the intestinal epithelium. This mucus is a dynamic semipermeable barrier and one of the first-line defense mechanisms against the outside environment, protecting the body against chemical, mechanical, or biological external insults. At the same time, the intestinal mucus accommodates the resident microbiota, providing nutrients and attachment sites, and therefore playing an essential role in the host–pathogen interactions and gut homeostasis. Underneath this mucus layer, the intestinal epithelium is organized into finger-like protrusions called villi and invaginations called crypts. This characteristic 3D architecture is known to influence the epithelial cell differentiation and function. However, when modelling in vitro the intestinal host–pathogen interactions, these two essential features, the intestinal mucus and the 3D topography are often not represented, thus limiting the relevance of the models. Here we present an in vitro model that mimics the small intestinal mucosa and its interactions with intestinal pathogens in a relevant manner, containing the secreted mucus layer and the epithelial barrier in a 3D villus-like hydrogel scaffold. This 3D architecture significantly enhanced the secretion of mucus. In infection with the pathogenic adherent invasive E. coli strain LF82, characteristic of Crohn’s disease, we observed that this secreted mucus promoted the adhesion of the pathogen and at the same time had a protective effect upon its invasion. This pathogenic strain was able to survive inside the epithelial cells and trigger an inflammatory response that was milder when a thick mucus layer was present. Thus, we demonstrated that our model faithfully mimics the key features of the intestinal mucosa necessary to study the interactions with intestinal pathogens.

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“…Not surprisingly, most pathogens can readily permeate through mucus, including viruses (e.g., HIV, 18 , 19 HSV, 20 , 21 HPV, 18 Norwalk, 18 etc.) and bacteria possessing active motility (e.g., H. pylori, 22 Salmonella, 23 , 24 etc.). Importantly, pathogens have evolved surfaces that do not adhere to mucin fibers, typically by having minimal exposed hydrophobic surfaces and with hydrophilic surfaces that are anionic, or are highly charged but neutral.…”

Section: Biophysical Properties Of Mucus and The Need For Adaptive Im...mentioning

confidence: 99%

The biophysical principles underpinning muco-trapping functions of antibodies

Schaefer

Lai

2021

Human Vaccines & Immunotherapeutics

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In addition to the classical immunological functions such as neutralization, antibody-dependent cellular cytotoxicity, and complement activation, IgG antibodies possess a little-recognized and under-utilized effector function at mucosal surfaces: trapping pathogens in mucus. IgG can potently immobilize pathogens that otherwise readily diffuse or actively swim through mucus by forming multiple low-affinity bonds between the array of pathogen-bound antibodies and the mucin mesh. Trapping in mucus can exclude pathogens from contacting target cells, and facilitate their rapid elimination by natural mucus clearance mechanisms. Despite the fact that most infections are transmitted at mucosal surfaces, this muco-trapping effector function has only been revealed within the past decade, with the evidence to date suggesting that it is a universal effector function of IgG-Fc capable of immobilizing both viral and highly motile bacterial pathogens in all major mucosal secretions. This review provides an overview of the current evidence for Fc-mucin crosslinking as an effector function for antibodies in mucus, the mechanism by which the accumulation of weak Fc-mucin bonds by IgG bound to the surface of a pathogen can result in immobilization of antibody-pathogen complexes, and how trapping in mucus can contribute to protection against foreign pathogens.

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Mucus blocks probiotics but increases penetration of motile pathogens and induces TNF‐α and IL‐8 secretion

Cited by 5 publications

References 59 publications

Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells

Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells

Mimicking the Intestinal Host–Pathogen Interactions in a 3D In Vitro Model: The Role of the Mucus Layer

The biophysical principles underpinning muco-trapping functions of antibodies

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