Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology

Fujiwara, Hideaki; Seike, Keisuke; Brooks, Michael; Mathew, Anna V.; Kovalenko, Ilya; Pal, Anupama; Lee, Ho‐Joon; Peltier, Daniel; Kim, Stephanie; Liu, Chen; Oravecz-Wilson, Katherine; Li, Lü; Sun, Yaping; Byun, Jaeman; Maeda, Yoshinobu; Wicha, Max S.; Saunders, Thomas L.; Rehemtulla, Alnawaz; Lyssiotis, Costas A.; Pennathur, Subramaniam; Reddy, Pavan

doi:10.1038/s41590-021-01048-3

Cited by 22 publications

(13 citation statements)

References 67 publications

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“…It has been demonstrated that E. coli infection on ducks causes damage to the intestinal barrier and subsequently triggers mucosal inflammatory responses, which is an energy-consuming process ( Pi et al., 2014 ). The mitochondrion plays a central role in energy metabolism homeostasis through the respiratory chain, and ATP synthesis takes place in the mitochondria by oxidative phosphorylation ( Ashton et al., 2018 ; Fujiwara et al., 2021 ). Our results showed that oxidative phosphorylation complexes downregulated the genes and reduced the mitochondrial oxidative phosphorylation activity in jejunum tissue, resulting in impaired mitochondrial function by E. coli infection.…”

Section: Discussionmentioning

confidence: 99%

Escherichia coli O88 induces intestinal damage and inflammatory response through the oxidative phosphorylation and ribosome pathway in Pekin ducks

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

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Colibacillosis is one of the major health threats in the poultry industry worldwide. Understanding the pathogenic mechanisms involved in Escherichia coli-induced inflammatory response may lead to the development of new therapies to combat the disease. To address this, a total of 96 1-day-old male lean Pekin ducklings were employed and randomly allocated to two treatments, each with six replicates of eight ducks. Ducks in the experiment group (EG) and the control group (CG) were separately orally administered with 0.2 ml of pathogenic E. coli O88 (3 × 109 CFU/ml) or equivalent volumes of 0.9% sterile saline solution on day 7, two times with an 8-h interval. Serum and intestinal samples were collected on days 9, 14, and 28. Results showed that ducks challenged with E. coli had lower average daily gain and higher feed intake/weight gain during days 9–14 and overall (P < 0.05). Histopathological examination showed that E. coli decreased the villus height and the ratio of villus height/crypt depth in the jejunum (P < 0.05) on days 9 and 14. The intestinal barrier was disrupted, presenting in E. coli ducks having higher serum DAO and D-LA on days 9 and 14 (P < 0.05) and greater content of serum LPS on day 9 (P < 0.05). Escherichia coli infection also triggered a systemic inflammatory response including the decrease of the serum IgA, IgM, and jejunal sIgA on day 14 (P < 0.05). In addition to these, 1,062 differentially expressed genes were detected in the jejunum tissues of ducks by RNA-seq, consisting of 491 upregulated and 571 downregulated genes. Based on the KEGG database, oxidative phosphorylation and the ribosome pathway were the most enriched. These findings reveal the candidate pathways and genes that may be involved in E. coli infection, allow a better understanding of the molecular mechanisms of inflammation progression and may facilitate the genetic improvement of ducks, and provide further insights to tackle the drug sensitivity and animal welfare issues.

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Section: Discussionmentioning

confidence: 99%

Escherichia coli O88 induces intestinal damage and inflammatory response through the oxidative phosphorylation and ribosome pathway in Pekin ducks

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

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“…The mitochondrion plays a central role in energy metabolism homeostasis through the respiratory chain. ATP synthesis takes place in the mitochondria by oxidative phosphorylation [ 54 , 55 ]. Mitochondrial oxidative phosphorylation contributes to producing enough ATP for the body to use [ 56 ], and once this process is disrupted and ATP synthesis is also affected [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Bacillus subtilis Protects the Ducks from Oxidative Stress Induced by Escherichia coli: Efficacy and Molecular Mechanism

Yang

et al. 2022

Antioxidants

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Bacillus. subtilis has been widely used in animal husbandry as a potential alternative to antibiotics due to its excellent bacteriostasis and antioxidant activity. This study aims to investigate the effects of Bacillus. subtilis on the protection of ducks from Escherichia coli infection and its mechanism. The four experimental groups include the negative control group, positive control group, antibiotic group and Bacillus. subtilis group. Ducks in positive, antibiotic and Bacillus. subtilis groups are orally administered with Escherichia coli and equivalent saline solution for the negative group. The results show that supplements with Bacillus. subtilis enhances the performance and health status of the infected ducks. Moreover, Bacillus. subtilis alleviates the increase in globulin, LPS and MDA, and the decrease in albumin, T-AOC and T-SOD in the serum caused by Escherichia coli infection. Bacillus. subtilis also attenuates injury in the intestine and partially reverses the increase in ROS production and the depletion of ATP in the jejunum. These effects are accompanied with the change of related genes of the ribosome (13.54%) and oxidative phosphorylation (6.68%). Collectively, Bacillus. subtilis alleviates the damage caused by Escherichia coli infection in ducks by activating ribosome and oxidative phosphorylation signaling to regulate antioxidant and energy metabolism.

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“…Mechanistically, GVHD improvement via butyrate in a mouse model is dependent upon the presence of SCFA receptor GRP43 (118). Additionally, butyrate ameliorated the metabolic defect of reduced succinate dehydrogenase A (SDHA) in allogeneic intestinal epithelial cells (IECs), which in turn reduced the severity of GVHD (119). Another study showed that high butyrate-producing organisms Clostridia increased intestinal Tregs, and those Tregs are involved in modulating gut inflammation response through several mechanisms (i.e., IL-10 release) (120,121) that decreased Gut-GVHD and increased survival after allo-HSCT (113).…”

Section: Microbial Community and Their Metabolites In Regulating Ster...mentioning

confidence: 99%

Steroid-Refractory Gut Graft-Versus-Host Disease: What We Have Learned From Basic Immunology and Experimental Mouse Model

2022

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Intestinal graft-versus-host disease (Gut-GVHD) is one of the major causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While systemic glucocorticoids (GCs) comprise the first-line treatment option, the response rate for GCs varies from 30% to 50%. The prognosis for patients with steroid-refractory acute Gut-GVHD (SR-Gut-aGVHD) remains dismal. The mechanisms underlying steroid resistance are unclear, and apart from ruxolitinib, there are no approved treatments for SR-Gut-aGVHD. In this review, we provide an overview of the current biological understanding of experimental SR-Gut-aGVHD pathogenesis, the advanced technology that can be applied to the human SR-Gut-aGVHD studies, and the potential novel therapeutic options for patients with SR-Gut-aGVHD.

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Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology

Cited by 22 publications

References 67 publications

Escherichia coli O88 induces intestinal damage and inflammatory response through the oxidative phosphorylation and ribosome pathway in Pekin ducks

Escherichia coli O88 induces intestinal damage and inflammatory response through the oxidative phosphorylation and ribosome pathway in Pekin ducks

Bacillus subtilis Protects the Ducks from Oxidative Stress Induced by Escherichia coli: Efficacy and Molecular Mechanism

Steroid-Refractory Gut Graft-Versus-Host Disease: What We Have Learned From Basic Immunology and Experimental Mouse Model

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