Microbes exploit death-induced nutrient release by gut epithelial cells

Anderson, Christopher J.; Medina, Christopher B.; Barron, Brady; Karvelyte, Laura; Aaes, Tania Løve; Lambertz, Irina; Perry, Justin C.; Mehrotra, Parul; Gonçalves, Amanda; Lemeire, Kelly; Blancke, Gillian; Andries, Vanessa; Ghazavi, Farzaneh; Martens, Arne; Loo, Geert; Vereecke, Lars; Vandenabeele, Peter; Ravichandran, Kodi S.

doi:10.1038/s41586-021-03785-9

Cited by 66 publications

(53 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AIEC penetrate the mucus layer and adhere to intestinal epithelial cells through FimH and cell adhesion molecule 6 (Ceacam 6), and then colonize in the intestinal mucosa ( Palmela et al., 2018 ). Enterobacteriaceae can use soluble factors released by apoptotic intestinal epithelial cells to promote the growth and colonization by driving the pyruvate formate-lyase-encoding pflB gene to induce the deterioration of IBD ( Anderson et al., 2021 ). Klebsiella pneumoniae invades intestinal epithelial cells and interacts with macrophages to drive the release of interleukin (IL)-1β and tumor necrosis factor (TNF) ( Read et al., 2021 ).…”

Section: Microbiota Interact With the Intestinal Epithelial Barrier I...mentioning

confidence: 99%

The Gut Microbiota in Inflammatory Bowel Disease

Qiu

Ishimoto

et al. 2022

Front. Cell. Infect. Microbiol.

214

View full text Add to dashboard Cite

Epidemiological surveys indicate that the incidence of inflammatory bowel disease (IBD) is increasing rapidly with the continuous growth of the economy. A large number of studies have investigated the relationship between the genetic factors related to the susceptibility to IBD and the gut microbiota of patients by using high-throughput sequencing. IBD is considered the outcome of the interaction between host and microorganisms, including intestinal microbial factors, abnormal immune response, and a damaged intestinal mucosal barrier. The imbalance of microbial homeostasis leads to the colonization and invasion of opportunistic pathogens in the gut, which increases the risk of the host immune response and promotes the development of IBD. It is critical to identify the specific pathogens related to the pathogenesis of IBD. An in-depth understanding of various pathogenic factors is of great significance for the early detection of IBD. This review highlights the role of gut microbiota in the pathogenesis of IBD and provides a theoretical basis for the personalized approaches that modulate the gut microbiota to treat IBD.

show abstract

Section: Microbiota Interact With the Intestinal Epithelial Barrier I...mentioning

confidence: 99%

The Gut Microbiota in Inflammatory Bowel Disease

Qiu

Ishimoto

et al. 2022

Front. Cell. Infect. Microbiol.

214

View full text Add to dashboard Cite

show abstract

“…However, our data do not exclude a particularly important role of apoptosis in tolerance induction, microbiome shaping, tissue repair by apoptosis-induced proliferation during challenges, and control of intestinal infection. Indeed, a crucial role for apoptosis in IECs was demonstrated during different challenges, e.g., tolerance induction during barrier loss ( 17 ), modulation of anticancer immunosurveillance during chemotherapy ( 59 ), sensitivity to Clostridium difficile infection ( 58 ), and IEC apoptosis-dependent boosting of growth of multiple Enterobacteriaceae during dysbiosis ( 69 ). Recently the unique role of apoptosis during steady-state regeneration was shown in hair follicle stem cell (HFSC) self-renewal and differentiation.…”

Section: Discussionmentioning

confidence: 99%

Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state

Ghazavi

Huysentruyt

Coninck

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Apoptosis is widely believed to be crucial for epithelial cell death and shedding in the intestine, thereby shaping the overall architecture of the gastrointestinal tract, but also regulating tolerance induction, pinpointing a role of apoptosis intestinal epithelial cell (IEC) turnover and maintenance of barrier function, and in maintaining immune homeostasis. To experimentally address this concept, we generated IEC-specific knockout mice that lack both executioner caspase-3 and caspase-7 (Casp3/7ΔIEC), which are the converging point of the extrinsic and intrinsic apoptotic pathway. Surprisingly, the overall architecture, cellular landscape, and proliferation rate remained unchanged in these mice. However, nonapoptotic cell extrusion was increased in Casp3/7ΔIEC mice, compensating apoptosis deficiency, maintaining the same physiological level of IEC shedding. Microbiome richness and composition stayed unaffected, bearing no sign of dysbiosis. Transcriptome and single-cell RNA sequencing analyses of IECs and immune cells revealed no differences in signaling pathways of differentiation and inflammation. These findings demonstrate that during homeostasis, apoptosis per se is dispensable for IEC turnover at the top of intestinal villi intestinal tissue dynamics, microbiome, and immune cell composition.

show abstract

“…In this context, we make the surprising finding that presence of GzmB increased susceptibility to Salmonella infection, rather than providing protection. This seemingly counter-intuitive finding could be explained by recent evidence showing that apoptosis of intestinal epithelial cells supports the growth of Salmonella, by providing catabolic nutrients (Anderson et al, 2021). Thus, the induction of apoptosis of infected epithelial cells by GzmB could support the growth of Salmonella.…”

Section: Discussionmentioning

confidence: 99%

Distinct cell death pathways induced by granzymes collectively protect against intestinalSalmonellainfection

Vandereyken

Chawla

Arias

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

SUMMARYThe cytotoxic proteases Granzymes A (GzmA) and B (GzmB) are important components of the arsenal used by cytotoxic immune cells to kill virally infected/damaged cells. Until now, there has been limited evidence that GzmA/B proteins contribute to combating intracellular bacterial pathogens in mammals. Here, we find that the route of infection of the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium reveals the distinct roles that Granzymes play in defending against bacterial infection. We used Gzma-/-Gzmb-/- mice to discover that Granzymes are required to protect mice against oral infection with Salmonella. However, Granzymes do not play a role in systemic infection. We investigated the tissue-specific expression of Granzymes and determined that intestinal intraepithelial lymphocytes (IEL) are the only cell types that express Granzymes in healthy non-infected mice. In fact, IEL are sufficient to mediate the protective effects of Granzymes against Salmonella infection. Intriguingly, we found that GzmA and GzmB play opposing roles in Salmonella control, with GzmA being protective against infection whilst GzmB promoted infection. Both GzmA and GzmB proteins functioned independently of the pore-forming molecule Perforin, suggesting extracellular action. Our study reveals that IEL-expressed Granzymes play significant and distinct functions in host defense from oral bacterial infection.

show abstract

Microbes exploit death-induced nutrient release by gut epithelial cells

Cited by 66 publications

References 48 publications

The Gut Microbiota in Inflammatory Bowel Disease

The Gut Microbiota in Inflammatory Bowel Disease

Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state

Distinct cell death pathways induced by granzymes collectively protect against intestinalSalmonellainfection

Contact Info

Product

Resources

About