Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Differential expression of innate immune and metabolic genes in LPS-challenged chickens

ABSTRACT: Salmonella causes inflammation in infected hosts. Inflammation is a well-characterized defensive mechanism of innate immunity. The recognition and engagement of lipopolysaccharide (LPS) endotoxins in the outer membranes of Salmonella to Toll-like receptor 4 of immune cells (macrophages and dendritic cells) trigger inflammatory responses characterized by secretion of pro-inflammatory cytokines, including TNF-beta, IL-1 and IL-6. These cytokines cause fever, anorexia, bodyweight losses, and catabolism of skeletal muscles and adipose tissues. However, molecular events underlying innate immune responses and metabolic activities during the later stage of inflammation are poorly understood. Additionally, the effects of prebiotics and antibiotics on innate immunity and nutrient metabolism are not yet reported. The objective of this study is to investigate the effects of a mannanoligosaccharide (MOS) prebiotic and virginiamycin (VIRG) sub-therapeutic antibiotic on innate immunity and glucose metabolism during late inflammation. We induced Salmonella LPS-systemic inflammation in a chicken model. Differentially regulated gene expressions were measured using 2 colour focussed oligonucleotide chicken-specific microarrays. Microarray analysis was performed on liver, intestinal and skeletal muscle tissues. We found that late inflammation was principally modulated by interleukin 3 (IL 3) and that glucose was mobilized from gluconeogenesis occurring in the intestines only. MOS and VIRG modulated innate immunity and metabolic genes differently. In contrast to VIRG, MOS terminated inflammatory responses earlier. Our results indicate IL 3 gene up-regulation in VIRG-fed chickens. To meet the higher energy requirements of VIRG chickens, genes for intestinal gluconeogenesis and liver glycolysis were respectively induced. Our study reveals the potential mechanisms by which prebiotic and antibiotic modulated innate immunity and glucose metabolism during late inflammation. 14-day old chickens were injected i.p. with saline or LPS. For each tissue and experimental conditions (saline or LPS challenge), a total of 12 microarrays (6 MOS birds + 6 VIRG birds) were used in a 2 x 2 factorial design and complete interwoven loop arrangement. We compared gene expression from prebiotic-fed birds with antibiotic-fed birds without including reference RNA. LPS challenge, antibiotic or prebiotic, innate immunity, glucose metabolism

ORGANISM(S): Gallus gallus

SUBMITTER: Bushansingh Baurhoo

PROVIDER: E-GEOD-28959 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Salmonella causes inflammation in infected hosts. Inflammation is a well-characterized defensive mechanism of innate immunity. The recognition and engagement of lipopolysaccharide (LPS) endotoxins in the outer membranes of Salmonella to Toll-like receptor 4 of immune cells (macrophages and dendritic cells) trigger inflammatory responses characterized by secretion of pro-inflammatory cytokines, including TNF-beta, IL-1 and IL-6. These cytokines cause fever, anorexia, bodyweight losses, and catabolism of skeletal muscles and adipose tissues. However, molecular events underlying innate immune responses and metabolic activities during the later stage of inflammation are poorly understood. Additionally, the effects of prebiotics and antibiotics on innate immunity and nutrient metabolism are not yet reported. The objective of this study is to investigate the effects of a mannanoligosaccharide (MOS) prebiotic and virginiamycin (VIRG) sub-therapeutic antibiotic on innate immunity and glucose metabolism during late inflammation. We induced Salmonella LPS-systemic inflammation in a chicken model. Differentially regulated gene expressions were measured using 2 colour focussed oligonucleotide chicken-specific microarrays. Microarray analysis was performed on liver, intestinal and skeletal muscle tissues. We found that late inflammation was principally modulated by interleukin 3 (IL 3) and that glucose was mobilized from gluconeogenesis occurring in the intestines only. MOS and VIRG modulated innate immunity and metabolic genes differently. In contrast to VIRG, MOS terminated inflammatory responses earlier. Our results indicate IL 3 gene up-regulation in VIRG-fed chickens. To meet the higher energy requirements of VIRG chickens, genes for intestinal gluconeogenesis and liver glycolysis were respectively induced. Our study reveals the potential mechanisms by which prebiotic and antibiotic modulated innate immunity and glucose metabolism during late inflammation.

Project description:Kaiser2014 - Salmonella persistence after ciprofloxacin treatment The model describes the bacterial tolerance to antibiotics. Using a mouse model for Salmonella diarrhea, the authors have found that bacterial persistence occurs in the presence of the antibiotic ciprofloxacin because Salmonella can exist in two different states. One, the fast-growing population that spreads in the host's tissues and the other, slow-growing "persister" population that hide out inside dendritic cells of the host's immune system and cannot be attacked by the antibiotics. However, this can be killed by adding agents that directly stimulate the host's immune defense. This model is described in the article: Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment. Kaiser P, Regoes RR, Dolowschiak T, Wotzka SY, Lengefeld J, Slack E, Grant AJ, Ackermann M, Hardt WD. PLoS Biol. 2014 Feb 18;12(2):e1001793. Abstract: In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics. This model is hosted on BioModels Database and identified by: MODEL1312170001. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Differential expression of innate immune and metabolic genes in LPS-challenged chickens

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