Inflammasomes induce sepsis following community breakdown

Bordon, Yvonne

doi:10.1038/nri3235

Cited by 23 publications

(22 citation statements)

References 1 publication

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“…The specific mechanisms linking the intestinal microbial changes to sepsis remain unclear, but recent studies implicating disruption of the normal intestinal microbiota and induction of inflammasome are intriguing as potential mechanisms. [24], [25].…”

Section: Discussionmentioning

confidence: 99%

Distortions in Development of Intestinal Microbiota Associated with Late Onset Sepsis in Preterm Infants

et al. 2013

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Late onset sepsis (LOS) is a major contributor to neonatal morbidity and mortality, especially in premature infants. Distortions in the establishment of normal gut microbiota, commensal microbes that colonize the digestive tract, might increase the risk of LOS via disruption of the mucosal barrier with resultant translocation of luminal contents. Correlation of distortions of the intestinal microbiota with LOS is a necessary first step to design novel microbiota-based screening approaches that might lead to early interventions to prevent LOS in high risk infants. Using a case/control design nested in a cohort study of preterm infants, we analyzed stool samples that had been prospectively collected from ten preterm infants with LOS and from 18 matched controls. A 16S rRNA based approach was utilized to compare microbiota diversity and identify specific bacterial signatures that differed in their prevalence between cases and controls. Overall α-diversity (Chao1) was lower in cases two weeks before (p<0.05) but not one week before or at the time of diagnosis of LOS. Overall microbiota structure (Unifrac) appeared distinct in cases 2 weeks and 1 week before but not at diagnosis (p<0.05). Although we detected few operational taxonomic units (OTUs) unique or enriched in cases, we found many OTUs common in controls that were lacking in cases (p<0.01). Bifidobacteria counts were lower in cases at all time points. Our results support the hypothesis that a distortion in normal microbiota composition, and not an enrichment of potential pathogens, is associated with LOS in preterm infants.

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Section: Discussionmentioning

confidence: 99%

Distortions in Development of Intestinal Microbiota Associated with Late Onset Sepsis in Preterm Infants

et al. 2013

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“…Moreover, neonates developing sepsis present a low microbial diversity compared to healthy infants [173]. The specific mechanisms linking the intestinal microbial changes to sepsis remain unclear, but recent studies favor the idea that disruption of the normal intestinal microbiota and induction of the inflammasome are potential mechanisms [174, 175]. Moreover, the number of Bifidobacteria ,known to colonize the healthy newborn intestine soon after birth and likely contribute to normal intestinal development, is lower in LONS infants compared to healthy controls [172, 176].…”

Section: Neonatal Innate Immune Response Infections and Sepsismentioning

confidence: 99%

Neonatal Immune Adaptation of the Gut and Its Role during Infections

Tourneur

Chassin

2013

Clinical and Developmental Immunology

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The intestinal tract is engaged in a relationship with a dense and complex microbial ecosystem, the microbiota. The establishment of this symbiosis is essential for host physiology, metabolism, and immune homeostasis. Because newborns are essentially sterile, the first exposure to microorganisms and environmental endotoxins during the neonatal period is followed by a crucial sequence of active events leading to immune tolerance and homeostasis. Contact with potent immunostimulatory molecules starts immediately at birth, and the discrimination between commensal bacteria and invading pathogens is essential to avoid an inappropriate immune stimulation and/or host infection. The dysregulation of these tight interactions between host and microbiota can be responsible for important health disorders, including inflammation and sepsis. This review summarizes the molecular events leading to the establishment of postnatal immune tolerance and how pathogens can avoid host immunity and induce neonatal infections and sepsis.

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“…Although sepsis has been extensively studied over the past decades, the mechanism underlying the significant pathophysiological alterations remains unclear. Accumulating evidence suggests that inflammasome, an intracellular multiprotein complex, is involved in the pathogenesis of sepsis [ 10 , 11 ]. The inflammasome triggered pyroptosis in a caspase-1-dependent manner [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…The inflammasome triggered pyroptosis in a caspase-1-dependent manner [ 12 , 13 ]. In sepsis, pyroptosis ruptures the plasma membrane, which results in releases of abundant inflammatory factors [ 10 – 15 ]. An obvious deficiency in the number of immunocytes, especially gastrointestinal epithelial cells, dendritic cells (DCs), lymphocytes, and even thymocytes, was observed in both septic animals and patients [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Molecular Mechanisms Underlying Pyroptosis in Sepsis

Gao

Zhai

Chai

2018

Mediators of Inflammation

115

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Sepsis is recognized as a life-threatening organ dysfunctional disease that is caused by dysregulated host responses to infection. Up to now, sepsis still remains a dominant cause of multiple organ dysfunction syndrome (MODS) and death among severe condition patients. Pyroptosis, originally named after the Greek words “pyro” and “ptosis” in 2001, has been defined as a specific programmed cell death characterized by release of inflammatory cytokines. During sepsis, pyroptosis is required for defense against bacterial infection because appropriate pyroptosis can minimize tissue damage. Even so, pyroptosis when overactivated can result in septic shock, MODS, or increased risk of secondary infection. Proteolytic cleavage of gasdermin D (GSDMD) by caspase-1, caspase-4, caspase-5, and caspase-11 is an essential step for the execution of pyroptosis in activated innate immune cells and endothelial cells stimulated by cytosolic lipopolysaccharide (LPS). Cleaved GSDMD also triggers NACHT, LRR, and PYD domain-containing protein (NLRP) 3-mediated activation of caspase-1 via an intrinsic pathway, while the precise mechanism underlying GSDMD-induced NLRP 3 activation remains unclear. Hence, this study provides an overview of the recent advances in the molecular mechanisms underlying pyroptosis in sepsis.

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Inflammasomes induce sepsis following community breakdown

Cited by 23 publications

References 1 publication

Distortions in Development of Intestinal Microbiota Associated with Late Onset Sepsis in Preterm Infants

Distortions in Development of Intestinal Microbiota Associated with Late Onset Sepsis in Preterm Infants

Neonatal Immune Adaptation of the Gut and Its Role during Infections

Recent Advances in the Molecular Mechanisms Underlying Pyroptosis in Sepsis

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