A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages

Danne, Camille; Ryzhakov, Grigory; Martínez-López, María; Ilott, Nicholas E.; Franchini, Fanny; Cuskin, Fiona; Lowe, Elisabeth C.; Bullers, Samuel J.; Arthur, J. Simon C.; Powrie, Fiona

doi:10.1016/j.chom.2017.11.002

Cited by 99 publications

(75 citation statements)

References 61 publications

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“…IL‐10 is a prototypical anti‐inflammatory cytokine which inhibits the synthesis of pro‐inflammatory cytokines such as TNF‐ɑ and IFN‐Ɣ thus limiting pathological cell shedding responses 30 . IL‐10 induction has previously been described to be driven by certain microbiota members such as Bacteroides , Bifidobacterium and Helicobacter , suggesting that specific members may play a key role for inducing anti‐inflammatory and anti‐apoptotic responses, thereby driving protective barrier integrity during the neonatal period 31-34 …”

Section: Discussionmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

et al. 2020

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The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect.Our findings further support the importance of the early life window for microbiotaepithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation. K E Y W O R D S antibiotics, cell shedding, early life, fecal microbiota transplant, inflammation, intestinal epithelium, metabolites, microbiota 7076 | HUGHES Et al.

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Section: Discussionmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

et al. 2020

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“…IL-10 is a prototypical anti-inflammatory cytokine which inhibits the synthesis of pro-inflammatory cytokines such as TNF-ɑ and IFN-Ɣ thus limiting pathological cell shedding responses [23]. IL-10 induction has previously been described to be driven by certain microbiota members such as Bacteroides, Bifidobacterium and Helicobacter, suggesting that specific members may play a key role for inducing anti-inflammatory and anti-apoptotic responses, thereby driving protective barrier integrity during the neonatal period [24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Hughes

Schofield

Dalby

et al. 2019

Preprint

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AbstractThe gut microbiota plays a crucial role in regulating and maintaining the epithelial barrier, particularly during early life. Notably, patients with chronic intestinal inflammation have a dysregulated process of renewal and replenishment of the intestinal epithelial cell (IEC) barrier, which is linked to disturbances in the gut microbiota. To date, there are no studies focussed on understanding the impact of inflammatory cell shedding events during the early life developmental window, and which host and microbial factors mediate these responses. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period (day 14, 21, 29 and week 8). Surprisingly neonatal mice (day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of LPS, with day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses, although we did observe that neonatal mice had elevated anti-inflammatory (IL-10) responses. Notably, when we profiled microbiota and metabolites from these mice, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Faecal microbiota transplant (FMT) and antibiotic studies confirmed the importance of early life gut microbiota in cell shedding responses. In these studies, neonates treated with antibiotics restored LPS-induced small intestinal cell shedding, whereas adult FMT alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlight areas for further investigation to probe underlying mechanisms to drive therapeutic development within the context of chronic inflammatory intestinal diseases.

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“…ROR γ t + Treg cells specific for Helicobacter hepaticus have also been shown to mediate tolerance to this commensal pathobiont, and a polysaccharide from the same species induces anti‐inflammatory IL‐10 secretion in intestinal macrophages . However, Helicobacter specificity itself does not dictate an anti‐inflammatory programme.…”

Section: Immune Cell–microbiota Crosstalkmentioning

confidence: 99%

“…120 RORct + Treg cells specific for Helicobacter hepaticus have also been shown to mediate tolerance to this commensal pathobiont, 121 and a polysaccharide from the same species induces anti-inflammatory IL-10 secretion in intestinal macrophages. 122 However, Helicobacter specificity itself does not dictate an anti-inflammatory programme. A recent study demonstrated that the same Helicobacter-specific T cells differentiate to Treg cells during homeostasis and effector T cells during colitis.…”

Section: Microbiota Modulation Of Intestinal Lymphocytesmentioning

confidence: 99%

Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity

2019

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Summary The intestinal epithelium forms a barrier between the microbiota and the rest of the body. In addition, beyond acting as a physical barrier, the function of intestinal epithelial cells (IECs) in sensing and responding to microbial signals is increasingly appreciated and likely has numerous implications for the vast network of immune cells within and below the intestinal epithelium. IECs also respond to factors produced by immune cells, and these can regulate IEC barrier function, proliferation and differentiation, as well as influence the composition of the microbiota. The mechanisms involved in IEC–microbe–immune interactions, however, are not fully characterized. In this review, we explore the ability of IECs to direct intestinal homeostasis by orchestrating communication between intestinal microbes and mucosal innate and adaptive immune cells during physiological and inflammatory conditions. We focus primarily on the most recent findings and call attention to the numerous remaining unknowns regarding the complex crosstalk between IECs, the microbiota and intestinal immune cells.

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A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages

Cited by 99 publications

References 61 publications

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity

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