Translocation of bacterial NOD2 agonist and its link with inflammation

Kim, Oh Yoen; Monsel, Antoine; Bertrand, Michèle; Cavaillon, Jean‐Marc; Coriat, Pierre; Adib‐Conquy, Minou

doi:10.1186/cc7980

Cited by 21 publications

(17 citation statements)

References 46 publications

(56 reference statements)

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“…These observations were in agreement with an earlier finding that systemic activation of the innate immune system by the gut microbiota involves recognition of meso-diaminopimelic acid (mesoDAP)-containing peptidoglycan found predominantly in Gram-negative bacteria, by the pattern recognition receptor nucleotide-binding, oligomerization domain-containing protein-1 (Nod1) [73]. Similarly abdominal surgery causes systemic release of Nod2-binding bacterial components and consequent rises in several inflammatory biomarkers [74].…”

Section: Regulation Of Innate Immunitysupporting

confidence: 92%

Microbiota, Immunoregulatory Old Friends and Psychiatric Disorders

Rook

Raison

Lowry

2014

Advances in Experimental Medicine and Biology

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Regulation of the immune system is an important function of the gut microbiota. Increasing evidence suggests that modern living conditions cause the gut microbiota to deviate from the form it took during human evolution. Contributing factors include loss of helminth infections, encountering less microbial biodiversity, and modulation of the microbiota composition by diet and antibiotic use. Thus the gut microbiota is a major mediator of the hygiene hypothesis (or as we prefer, "Old Friends" mechanism), which describes the role of organisms with which we co-evolved, and that needed to be tolerated, as crucial inducers of immunoregulation. At least partly as a consequence of reduced exposure to immunoregulatory Old Friends, many but not all of which resided in the gut, high-income countries are undergoing large increases in a wide range of chronic inflammatory disorders including allergies, autoimmunity and inflammatory bowel diseases. Depression, anxiety and reduced stress resilience are comorbid with these conditions, or can occur in individuals with persistently raised circulating levels of biomarkers of inflammation in the absence of clinically apparent peripheral inflammatory disease. Moreover poorly regulated inflammation during pregnancy might contribute to brain developmental abnormalities that underlie some cases of autism spectrum disorders and schizophrenia. In this chapter we explain how the gut microbiota drives immunoregulation, how faulty immunoregulation and inflammation predispose to psychiatric disease, and how psychological stress drives further inflammation via pathways that involve the gut and microbiota. We also outline how this two-way relationship between the brain and inflammation implicates the microbiota, Old Friends and immunoregulation in the control of stress resilience.

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Section: Regulation Of Innate Immunitysupporting

confidence: 92%

Microbiota, Immunoregulatory Old Friends and Psychiatric Disorders

Rook

Raison

Lowry

2014

Advances in Experimental Medicine and Biology

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“…The stimulation of PRRs by the microbiota in the intestine promote local innate defenses to bacterial infection at this site (17), and PRR ligands restore defective adaptive immunity to viral infection in the lung after microbiota depletion (33). Previous work also has shown that bacterial PRR ligands from the commensal microbiota are present in the circulation of normal healthy mice and humans (34,49,50). These PRR ligands bathe nonmucosal tissues and can enhance the antibacterial activity of bone marrow-derived neutrophils in ex vivo killing assays (34).…”

Section: Resultsmentioning

confidence: 99%

“…In contrast to TLRs, whose activation is tightly restrained in the intestine (65), NLRs are expressed in the intestinal mucosa and are activated by resident commensals (66), and this could result in the production of a signal originating from the intestinal mucosa that has a systemic effect on host lung function. Alternatively, peptidoglycan from the intestinal microbiota is found systemically in nonmucosal tissues of healthy mice and humans (including blood, spleen, and bone marrow) (34,49,50), and this disseminated peptidoglycan may activate underlying lung tissue to regulate alveolar macrophage function.…”

Section: Discussionmentioning

confidence: 99%

Early Innate Immunity to Bacterial Infection in the Lung Is Regulated Systemically by the Commensal Microbiota via Nod-Like Receptor Ligands

2014

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The commensal microbiota is a major regulator of the immune system. The majority of commensal bacteria inhabit the gastrointestinal tract and are known to regulate local mucosal defenses against intestinal pathogens. There is growing appreciation that the commensal microbiota also regulates immune responses at extraintestinal sites. Currently, however, it is unclear how this influences host defenses against bacterial infection outside the intestine. Microbiota depletion caused significant defects in the early innate response to lung infection by the major human pathogen Klebsiella pneumoniae. After microbiota depletion, early clearance of K. pneumoniae was impaired, and this could be rescued by administration of bacterial Nod-like receptor (NLR) ligands (the NOD1 ligand MurNAcTri DAP and NOD2 ligand muramyl dipeptide [MDP]) but not bacterial Toll-like receptor (TLR) ligands. Importantly, NLR ligands from the gastrointestinal, but not upper respiratory, tract rescued host defenses in the lung. Defects in early innate immunity were found to be due to reduced reactive oxygen species-mediated killing of bacteria by alveolar macrophages. These data show that bacterial signals from the intestine have a profound influence on establishing the levels of antibacterial defenses in distal tissues.

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“…They mediate activation of mitogen-activated protein kinases and NF-JB through a CARD-dependent recruitment of RIP2. 9,19,20 Kim et al 21 suggest that the presence of NOD2 agonist also contributes to the inflammatory response. In vitro, NOD2 has been found involved in the bacterial clearance of Salmonella and Streptococcus species.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that NOD2 is mainly expressed in antigen-presenting cells and epithelial cells. 21 Because PWBCs contain a large number of antigenpresenting cells such as dendritic cells and macrophages, 26,27 it is not surprising that a higher level of NOD2 was detected in PWBCs. In the pancreatic tissue directly exposed to inflammatory bacteria in the AP rats, NOD2 was found to be expressed at a relatively lower level.…”

Section: Discussionmentioning

confidence: 99%