Effect of Clostridium perfringens type C on TLR4/MyD88/NF-κB signaling pathway in piglet small intestines

Shi, Hairen; Huang, Xiaoyu; Yan, Zunqiang; Yang, Qiaoli; Wang, Pengfei; Li, Shenggui; Sun, Weibo; Gun, Shuangbao

doi:10.1016/j.micpath.2019.103567

Cited by 21 publications

(12 citation statements)

References 27 publications

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“…Gnotobiotic piglets with highly immature intestine also showed recruitment of inflammatory cells in the S. Typhimurium-infected ileum [47]. Lastly, intestinal TLR4 mRNA upregulation and HMGB1 protein levels were increased in both TLR4 and HMGB1 proteins in the pig ileal tissue 120 hrs after the infection with Clostridium perfringens type C [110]. Therefore, HMGB1 can serve as the marker of the damaged intestine.…”

Section: Discussionmentioning

confidence: 92%

High Mobility Group Box 1 and TLR4 Signaling Pathway in Gnotobiotic Piglets Colonized/Infected with L. amylovorus, L. mucosae, E. coli Nissle 1917 and S. Typhimurium

Šplı́chal

Donovan

Jenistova

et al. 2019

IJMS

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High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can be actively secreted by immune cells after different immune stimuli or passively released from cells undergoing necrosis. HMGB1 amplifies inflammation, and its hypersecretion contributes to multiple organ dysfunction syndrome and death. We tested possible immunomodulatory effect of commensal Lactobacillus amylovorus (LA), Lactobacillus mucosae (LM) or probiotic Escherichia coli Nissle 1917 (EcN) in infection of gnotobiotic piglets with Salmonella Typhimurium (ST). Transcription of HMGB1 and Toll-like receptors (TLR) 2, 4, and 9 and receptor for advanced glycation end products (RAGE), TLR4-related molecules (MD-2, CD14, and LBP), and adaptor proteins (MyD88 and TRIF) in the ileum and colon were measured by RT-qPCR. Expression of TLR4 and its related molecules were highly upregulated in the ST-infected intestine, which was suppressed by EcN, but not LA nor LM. In contrast, HMGB1 expression was unaffected by ST infection or commensal/probiotic administration. HMGB1 protein levels in the intestine measured by ELISA were increased in ST-infected piglets, but they were decreased by previous colonization with E. coli Nissle 1917 only. We conclude that the stability of HMGB1 mRNA expression in all piglet groups could show its importance for DNA transcription and physiological cell functions. The presence of HMGB1 protein in the intestinal lumen probably indicates cellular damage.

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Section: Discussionmentioning

confidence: 92%

High Mobility Group Box 1 and TLR4 Signaling Pathway in Gnotobiotic Piglets Colonized/Infected with L. amylovorus, L. mucosae, E. coli Nissle 1917 and S. Typhimurium

Šplı́chal

Donovan

Jenistova

et al. 2019

IJMS

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“…There were 14 pathways associated with immune responses, of which the NF- κ B signaling pathway [ 32 ], toll-like receptor signaling pathway [ 33 ], and JAK-STAT signaling pathway [ 34 ] are known to be associated with diarrhea caused by C. perfringens infection in animals. The above results indicated that C. perfringens type C elicited a strong immune response in the ileum tissue of the diarrheal piglets.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of MAPK Signaling Pathway Genes and Associated lncRNAs in the Ileum of Piglets Infected by Clostridium perfringens Type C

Luo

Huang

Yan

et al. 2020

BioMed Research International

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Clostridium perfringens type C (C. perfringens type C) is one of the main microbial pathogens responsible for piglet diarrhea worldwide, causing substantial economic losses for pig-rearing industries. The mitogen-activated protein kinase (MAPK) signaling pathway is a key regulator of inflammatory bowel disease, especially necrotic enteritis. However, whether and how the MAPK signaling pathway is involved in regulating the process of piglet diarrhea when challenged by C. perfringens type C are still unknown. Here, we screened 38 differentially expressed genes (DEGs) in piglets’ ileum tissues experimentally infected with C. perfringens type C that were enriched in the Sus scrofa MAPK signaling pathway, based on our previous transcriptome data. Of these DEGs, 12 genes (TRAF2, MAPK8, and GADD45G, among others) were upregulated whereas 26 genes (MAPK1, TP53, and CHUK, among others) were downregulated in the infected group. Our results showed that MAPK1, TP53, MAPK8, MYC, and CHUK were in the core nodes of the PPI network. Additionally, we obtained 35 lncRNAs from the sequencing data, which could be trans-targeted to MAPK signaling pathway genes and were differentially expressed in the ileum tissues infected with C. perfringens. We used qRT-PCR to verify the expression levels of genes and lncRNAs related to the MAPK signaling pathway; their expression patterns were consistent with RNA sequencing data. Our results provide strong support for deeply exploring the role of the MAPK signaling pathway in diarrhea caused by C. perfringens type C.

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“…Under experimental conditions, interleukin 6 and TNF-α co-stimulate naive CD8 T cells, resulting in strong cytolytic activity [63]. TLR4 and its downstream signaling pathways play a pivotal role for inducing the secretion of in ammatory cytokines during bacterial infection [64,65]. Shi et al reported that the levels of IL-6 and IL-2 in the gut were increased in piglets orally infected with C. perfringens type C [64].…”

Section: Discussionmentioning

confidence: 99%

“…TLR4 and its downstream signaling pathways play a pivotal role for inducing the secretion of in ammatory cytokines during bacterial infection [64,65]. Shi et al reported that the levels of IL-6 and IL-2 in the gut were increased in piglets orally infected with C. perfringens type C [64]. However, the results from our study showed that there was no signi cant difference in the secretion of pro-in ammatory cytokines in the diseased goats compared with healthy goats, both for IL-2 and IL-6, although the level of IL-2 was signi cantly higher in the ileum homogenate in the diseased goats.…”

Section: Discussionmentioning

confidence: 99%

Changes of Intestinal Oxidative Stress, Inflammation, and Gene Expression in Neonatal Goats Suffering from a Cold

Cheng

Yang

Tan

et al. 2020

Preprint

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Abstract Background Disease and disorders in young goats are serious threats to the animals’ health, and they influence the profitability of the goat industry. There is a need to better understand the potential biomarkers that can reflect the mortality and morbidity in young goats. Since gastrointestinal infection is probably the first ailment in young goats, the objective of this study was to explore the changes in oxidative stress, inflammation, and gene expression in the gastrointestinal tract of neonatal goats suffering from a cold. Results The activity of glutathione peroxidase (GSH-Px) was less (P < 0.05) in the jejunum in neonatal goats suffering from a cold compared with healthy neonatal goats. However, the malondialdehyde (MDA) activities in the jejunum and ileum were higher (P < 0.05) in neonatal goats suffering from a cold compared with healthy neonatal goats. There was no significant difference in the super-oxide dismutase (SOD) and catalase (CAT) activity observed between the two groups (P > 0.05). For the concentrations of intestinal interleukin-2 (IL2) and interleukin-6 (IL6), only the IL-2 in ileum in the neonatal goats suffering from a cold was higher than that from healthy neonatal goats. Real-time PCR results showed that the expression of most toll-like receptor-4-(TLR4) pathway-related genes was similar in the two groups. The transcriptomic analysis of the jejunum showed a total of 364 differential expression genes (DEGs) identified in neonatal goats suffering from a cold compared with healthy neonatal goats. The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of up-regulated DEG was mainly related to the ECM−receptor interaction, pathways in cancer and axon guidance, and the down-regulated DEG mainly related to the arachidonic acid metabolism, complement, and coagulation cascades, and the Ras signaling pathway. Conclusions These results suggest that neonatal goats suffering from a cold experienced a higher intestinal oxidative stress compared with healthy neonatal goats. Thus, it is possible that the antioxidant capacity of young ruminants acts as an indicator of health status and the measurements of oxidation stress may be useful as diagnostic biomarkers, reflecting the mortality and morbidity in young goats.

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Effect of Clostridium perfringens type C on TLR4/MyD88/NF-κB signaling pathway in piglet small intestines

Cited by 21 publications

References 27 publications

High Mobility Group Box 1 and TLR4 Signaling Pathway in Gnotobiotic Piglets Colonized/Infected with L. amylovorus, L. mucosae, E. coli Nissle 1917 and S. Typhimurium

High Mobility Group Box 1 and TLR4 Signaling Pathway in Gnotobiotic Piglets Colonized/Infected with L. amylovorus, L. mucosae, E. coli Nissle 1917 and S. Typhimurium

Identification and Characterization of MAPK Signaling Pathway Genes and Associated lncRNAs in the Ileum of Piglets Infected by Clostridium perfringens Type C

Changes of Intestinal Oxidative Stress, Inflammation, and Gene Expression in Neonatal Goats Suffering from a Cold

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