{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:33:14Z","timestamp":1793194394022,"version":"4.5.0"},"reference-count":95,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T00:00:00Z","timestamp":1598140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","award":["COST LD15090"],"award-info":[{"award-number":["COST LD15090"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","award":["CZ.02.1.01\/0.0\/0.0\/16_025\/0007404"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_025\/0007404"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mikrobiologick\u00fd \u00fastav AV \u010cR","award":["Institutional Research Concept RVO 61388971"],"award-info":[{"award-number":["Institutional Research Concept RVO 61388971"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Salmonella Typhimurium is a Gram-negative bacterium that causes enterocolitis in humans and pigs. Lipopolysaccharide (LPS) is a component of the outer leaflet of Gram-negative bacteria that provokes endotoxin shock. LPS can be synthesized completely or incompletely and creates S (smooth) or R (rough) chemotypes. Toll-like receptors (TLR) 2, 4, and 9 initiate an inflammatory reaction to combat bacterial infections. We associated\/challenged one-week-old gnotobiotic piglets with wild-type S. Typhimurium with S chemotype or its isogenic \u2206rfa mutants with R chemotype LPS. The wild-type S. Typhimurium induced TLR2 and TLR4 mRNA expression but not TLR9 mRNA expression in the ileum and colon of one-week-old gnotobiotic piglets 24 h after challenge. The TLR2 and TLR4 stimulatory effects of the S. Typhimurium \u2206rfa mutants were related to the completeness of their LPS chain. The transcription of IL-12\/23 p40, IFN-\u03b3, and IL-6 in the intestine and the intestinal and plasmatic levels of IL-12\/23 p40 and IL-6 but not IFN-\u03b3 were related to the activation of TLR2 and TLR4 signaling pathways. The avirulent S. Typhimurium \u2206rfa mutants are potentially useful for modulation of the TLR2 and TLR4 signaling pathways to protect the immunocompromised gnotobiotic piglets against subsequent infection with the virulent S. Typhimurium.<\/jats:p>","DOI":"10.3390\/toxins12090545","type":"journal-article","created":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T21:28:06Z","timestamp":1598218086000},"page":"545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Toll-Like Receptor 4 Signaling in the Ileum and Colon of Gnotobiotic Piglets Infected with Salmonella Typhimurium or Its Isogenic \u2206rfa Mutants"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3665-1377","authenticated-orcid":false,"given":"Igor","family":"Splichal","sequence":"first","affiliation":[{"name":"Laboratory of Gnotobiology, Institute of Microbiology, Czech Academy of Sciences, 549 22 Novy Hradek, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Rychlik","sequence":"additional","affiliation":[{"name":"Department of Immunology, Veterinary Research Institute, 621 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Splichalova","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Institute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague 4-Krc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Karasova","sequence":"additional","affiliation":[{"name":"Department of Immunology, Veterinary Research Institute, 621 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7428-7687","authenticated-orcid":false,"given":"Alla","family":"Splichalova","sequence":"additional","affiliation":[{"name":"Laboratory of Gnotobiology, Institute of Microbiology, Czech Academy of Sciences, 549 22 Novy Hradek, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.biochem.71.110601.135414","article-title":"Lipopolysaccharide endotoxins","volume":"71","author":"Raetz","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1016\/j.carres.2003.07.010","article-title":"Structure of bacterial lipopolysaccharides","volume":"338","author":"Caroff","year":"2003","journal-title":"Carbohydr. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1128\/jb.166.3.699-705.1986","article-title":"Lipopolysaccharide nomenclature--past, present, and future","volume":"166","author":"Hitchcock","year":"1986","journal-title":"J. Bacteriol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/chem.201403923","article-title":"Chemistry of lipid A: At the heart of innate immunity","volume":"21","author":"Molinaro","year":"2015","journal-title":"Chemistry"},{"key":"ref_5","first-page":"25","article-title":"Lipid A, the endotoxic center of bacterial lipopolysaccharides: Relation of chemical structure to biological activity","volume":"231","author":"Rietschel","year":"1987","journal-title":"Prog. Clin. Biol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.imbio.2007.11.008","article-title":"Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections: Benefits and hazards of LPS hypersensitivity","volume":"213","author":"Freudenberg","year":"2008","journal-title":"Immunobiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1002\/eji.200535593","article-title":"R-form LPS, the master key to the activation ofTLR4\/MD-2-positive cells","volume":"36","author":"Huber","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1126\/science.8153625","article-title":"Prevention of drug access to bacterial targets: Permeability barriers and active efflux","volume":"264","author":"Nikaido","year":"1994","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4725","DOI":"10.1128\/JB.181.16.4725-4733.1999","article-title":"Structures of gram-negative cell walls and their derived membrane vesicles","volume":"181","author":"Beveridge","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1097\/CCM.0b013e31819267fb","article-title":"Molecular biology of inflammation and sepsis: A primer","volume":"37","author":"Cinel","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nature01326","article-title":"The immunopathogenesis of sepsis","volume":"420","author":"Cohen","year":"2002","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1189\/jlb.0203082","article-title":"How we detect microbes and respond to them: The Toll-like receptors and their transducers","volume":"74","author":"Beutler","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/S1286-4579(01)01481-2","article-title":"Role of lipopolysaccharide susceptibility in the innate immune response to Salmonella typhimurium infection: LPS, a primary target for recognition of Gram-negative bacteria","volume":"3","author":"Freudenberg","year":"2001","journal-title":"Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.toxicon.2017.10.016","article-title":"Exotoxins and endotoxins: Inducers of inflammatory cytokines","volume":"149","author":"Cavaillon","year":"2018","journal-title":"Toxicon"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e10128","DOI":"10.15252\/emmm.201810128","article-title":"Sepsis therapies: Learning from 30 years of failure of translational research to propose new leads","volume":"12","author":"Cavaillon","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.21037\/jtd.2018.11.74","article-title":"Improving clinical outcomes in sepsis and multiple organ dysfunction through precision medicine","volume":"11","author":"Mehta","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/jcb.27547","article-title":"Recent advances in endotoxin tolerance","volume":"120","author":"Liu","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.immuni.2016.11.007","article-title":"Reconstruction of LPS transfer cascade reveals structural determinants within LBP, CD14, and TLR4-MD2 for efficient LPS recognition and transfer","volume":"46","author":"Ryu","year":"2017","journal-title":"Immunity"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.it.2017.05.001","article-title":"Lipopolysaccharide detection across the kingdoms of life","volume":"38","author":"Kagan","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1051\/vetres:2006006","article-title":"Role of intestinal epithelial cells in the innate immune defence of the pig intestine","volume":"37","author":"Oswald","year":"2006","journal-title":"Vet. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1385\/MB:19:3:279","article-title":"The biology of endotoxin","volume":"19","author":"Heine","year":"2001","journal-title":"Mol. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.immuni.2011.05.006","article-title":"Toll-like receptors and their crosstalk with other innate receptors in infection and immunity","volume":"34","author":"Kawai","year":"2011","journal-title":"Immunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nri.2015.8","article-title":"Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease","volume":"16","author":"Cao","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1038\/emm.2013.97","article-title":"Recognition of lipopolysaccharide pattern by TLR4 complexes","volume":"45","author":"Park","year":"2013","journal-title":"Exp. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"185ra64","DOI":"10.1126\/scitranslmed.3005544","article-title":"Targeting the TLR co-receptor CD14 with TLR2-derived peptides modulates immune responses to pathogens","volume":"5","author":"Raby","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1084\/jem.20101111","article-title":"CD14 is a coreceptor of Toll-like receptors 7 and 9","volume":"207","author":"Baumann","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s15010-018-1183-8","article-title":"Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): An international expert consensus initiative for improvement of animal modeling in sepsis","volume":"46","author":"Osuchowski","year":"2018","journal-title":"Infection"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/prca.201300099","article-title":"The pig as an animal model for human pathologies: A proteomics perspective","volume":"8","author":"Bassols","year":"2014","journal-title":"Proteom. Clin. Appl."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16161","DOI":"10.1038\/nmicrobiol.2016.161","article-title":"A reference gene catalogue of the pig gut microbiome","volume":"1","author":"Xiao","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev-animal-020518-115142","article-title":"Translational Advances in Pediatric Nutrition and Gastroenterology: New Insights from Pig Models","volume":"8","author":"Burrin","year":"2020","journal-title":"Annu. Rev. Anim Biosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.tim.2011.11.002","article-title":"The pig: A model for human infectious diseases","volume":"20","author":"Meurens","year":"2012","journal-title":"Trends Microbiol."},{"key":"ref_32","first-page":"2","article-title":"Modified Clinical Monitoring Assesment Criteria for Multi-Organ Failure during Bacteremia and Sepsis Progression in a Pig Model","volume":"1","author":"Waterhouse","year":"2018","journal-title":"Adv. Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3389\/fimmu.2014.00481","article-title":"Salmonella-host interactions-modulation of the host innate immune system","volume":"5","author":"Hurley","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Campos, J., Mourao, J., Peixe, L., and Antunes, P. (2019). Non-typhoidal Salmonella in the pig production chain: A comprehensive analysis of Its impact on human health. Pathogens, 8.","DOI":"10.3390\/pathogens8010019"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.coi.2011.06.004","article-title":"Salmonella typhimurium diarrhea: Switching the mucosal epithelium from homeostasis to defense","volume":"23","author":"Kaiser","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1128\/IAI.71.5.2839-2858.2003","article-title":"Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host","volume":"71","author":"Barthel","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/IAI.71.1.1-12.2003","article-title":"Molecular pathogenesis of Salmonella enterica serotype typhimurium-induced diarrhea","volume":"71","author":"Zhang","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1111\/jpc.13585","article-title":"Non-typhoidal Salmonella infections in children: Review of literature and recommendations for management","volume":"53","author":"Wen","year":"2017","journal-title":"J. Paediatr. Child. Health"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rai, B., Utekar, T., and Ray, R. (2014). Preterm delivery and neonatal meningitis due to transplacental acquisition of non-typhoidal Salmonella serovar montevideo. BMJ Case. Rep., 2014.","DOI":"10.1136\/bcr-2014-205082"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.mib.2018.07.007","article-title":"Standardization in host-microbiota interaction studies: Challenges, gnotobiology as a tool, and perspective","volume":"44","author":"Mooser","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ducarmon, Q.R., Zwittink, R.D., Hornung, B.V.H., van, S.W., Young, V.B., and Kuijper, E.J. (2019). Gut icrobiota and Colonization Resistance against Bacterial Enteric Infection. Microbiol. Mol. Biol. Rev., 83.","DOI":"10.1128\/MMBR.00007-19"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/s10875-010-9505-3","article-title":"Alarmin HMGB1 is released in the small intestine of gnotobiotic piglets infected with enteric pathogens and its level in plasma reflects severity of sepsis","volume":"31","author":"Splichalova","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.1365-2249.2010.04283.x","article-title":"Interference of Bifidobacterium choerinum or Escherichia coli Nissle 1917 with Salmonella Typhimurium in gnotobiotic piglets correlates with cytokine patterns in blood and intestine","volume":"163","author":"Splichalova","year":"2011","journal-title":"Clin. Exp. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1128\/IAI.71.4.2182-2191.2003","article-title":"Rapid protection of gnotobiotic pigs against experimental salmonellosis following induction of polymorphonuclear leukocytes by avirulent Salmonella enterica","volume":"71","author":"Foster","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"220","DOI":"10.3389\/fimmu.2018.00220","article-title":"Preterm life in sterile conditions: A study on preterm, germ-free piglets","volume":"9","author":"Splichalova","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1177\/0023677219836715","article-title":"Gnotobiotics: Past, present and future","volume":"53","author":"Basic","year":"2019","journal-title":"Lab. Anim."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.dci.2008.07.007","article-title":"Humoral and cellular factors of maternal immunity in swine","volume":"33","author":"Salmon","year":"2009","journal-title":"Dev. Comp. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"R179","DOI":"10.1530\/REP-16-0325","article-title":"The evolution of the placenta","volume":"152","author":"Roberts","year":"2016","journal-title":"Reproduction"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Galen, J.E., Buskirk, A.D., Tennant, S.M., and Pasetti, M.F. (2016). Live attenuated human Salmonella vaccine candidates: Tracking the pathogen in natural infection and stimulation of host immunity. Ecosal. Plus., 7.","DOI":"10.1128\/ecosalplus.esp-0010-2016"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4227","DOI":"10.1128\/IAI.05398-11","article-title":"III Effect of deletion of genes involved in lipopolysaccharide core and O-antigen synthesis on virulence and immunogenicity of Salmonella enterica serovar Typhimurium","volume":"79","author":"Kong","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cimid.2019.04.003","article-title":"Differences in immune responses of pigs vaccinated with Salmonella Typhimurium and S. Choleraesuis strains and challenged with S. Choleraesuis","volume":"65","author":"Chang","year":"2019","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/ni.3123","article-title":"Control of adaptive immunity by the innate immune system","volume":"16","author":"Iwasaki","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/35101614","article-title":"Complete genome sequence of Salmonella enterica serovar Typhimurium LT2","volume":"413","author":"McClelland","year":"2001","journal-title":"Nature"},{"key":"ref_54","first-page":"504","article-title":"Virulence of wild and mutant strains of Salmonella typhimurium in ligated intestinal segments of calves, pigs, and rabbits","volume":"48","author":"Clarke","year":"1987","journal-title":"Am. J. Vet. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5244","DOI":"10.1128\/iai.65.12.5244-5249.1997","article-title":"Cellular changes and cytokine expression in the ilea of gnotobiotic piglets resulting from peroral Salmonella typhimurium challenge","volume":"65","author":"Trebichavsky","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.imbio.2007.05.001","article-title":"Susceptibility of germ-free pigs to challenge with protease mutants of Salmonella enterica serovar Typhimurium","volume":"212","author":"Splichal","year":"2007","journal-title":"Immunobiology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1016\/j.vaccine.2006.02.054","article-title":"Attenuated aroA Salmonella enterica serovar Typhimurium does not induce inflammatory response and early protection of gnotobiotic pigs against parental virulent LT2 strain","volume":"24","author":"Trebichavsky","year":"2006","journal-title":"Vaccine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/01.shk.0000191337.01036.b7","article-title":"Porcine models of severe sepsis: Emphasis on porcine peritonitis","volume":"24","author":"Goldfarb","year":"2005","journal-title":"Shock"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"143","DOI":"10.4161\/viru.26083","article-title":"Animal models of sepsis","volume":"5","author":"Fink","year":"2014","journal-title":"Virulence"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1186\/cc8872","article-title":"Sepsis biomarkers: A review","volume":"14","author":"Pierrakos","year":"2010","journal-title":"Crit. Care"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0171-2985(11)80349-9","article-title":"Mechanisms of endotoxin shock and endotoxin hypersensitivity","volume":"187","author":"Galanos","year":"1993","journal-title":"Immunobiology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.vetimm.2004.09.001","article-title":"Protection of gnotobiotic pigs against Salmonella enterica serotype Typhimurium by rough mutant of the same serotype is accompanied by the change of local and systemic cytokine response","volume":"103","author":"Splichal","year":"2005","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Splichal, I., Donovan, S.M., Jenistova, V., Splichalova, I., Salmonova, H., Vlkova, E., Neuzil, B.V., Sinkora, M., Killer, J., and Skrivanova, E. (2019). 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. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246294"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Splichalova, A., Splichalova, Z., Karasova, D., Rychlik, I., Trevisi, P., Sinkora, M., and Splichal, I. (2019). Impact of the lipopolysaccharide chemotype of Salmonella enterica serovar Typhimurium on virulence in gnotobiotic piglets. Toxins, 11.","DOI":"10.3390\/toxins11090534"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Awoniyi, M., Miller, S.I., Wilson, C.B., Hajjar, A.M., and Smith, K.D. (2012). Homeostatic regulation of Salmonella-induced mucosal inflammation and injury by IL-23. PLoS. ONE., 7.","DOI":"10.1371\/journal.pone.0037311"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1515\/bmc-2018-0007","article-title":"Interferon-gamma (IFN-gamma): Exploring its implications in infectious diseases","volume":"9","author":"Kak","year":"2018","journal-title":"Biomol. Concepts"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Song, J., Park, D.W., Moon, S., Cho, H.J., Park, J.H., Seok, H., and Choi, W.S. (2019). Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: A prospective controlled study according to the Sepsis-3 definitions. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4618-7"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1093\/infdis\/jiy185","article-title":"Experimental Enteric Bacterial Infections in Pigs","volume":"218","author":"Splichal","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1096\/fj.09-140798","article-title":"CD14 inhibition efficiently attenuates early inflammatory and hemostatic responses in Escherichia coli sepsis in pigs","volume":"24","author":"Thorgersen","year":"2010","journal-title":"FASEB J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.vetimm.2006.11.012","article-title":"Expression of Toll-like receptors, interleukin 8, macrophage migration inhibitory factor, and osteopontin in tissues from pigs challenged with Salmonella enterica serovar Typhimurium or serovar Choleraesuis","volume":"115","author":"Burkey","year":"2007","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.vetimm.2008.12.027","article-title":"Expression of porcine Toll-like receptor 2, 4 and 9 gene transcripts in the presence of lipopolysaccharide and Salmonella enterica serovars Typhimurium and Choleraesuis","volume":"130","author":"Burkey","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1051\/vetres\/2009072","article-title":"Quantitative analysis of the immune response upon Salmonella typhimurium infection along the porcine intestinal gut","volume":"41","author":"Arce","year":"2010","journal-title":"Vet. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fimmu.2014.00316","article-title":"A comparative review of toll-like receptor 4 expression and functionality in different animal species","volume":"5","author":"Vaure","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.anaerobe.2015.05.002","article-title":"Chemical communication in the gut: Effects of microbiota-generated metabolites on gastrointestinal bacterial pathogens","volume":"34","author":"Vogt","year":"2015","journal-title":"Anaerobe"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.4049\/jimmunol.166.3.1938","article-title":"MD-2 enables Toll-like receptor 2 (TLR2)-mediated responses to lipopolysaccharide and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components","volume":"166","author":"Dziarski","year":"2001","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.1128\/IAI.71.10.6058-6062.2003","article-title":"Differential contribution of Toll-like receptors 4 and 2 to the cytokine response to Salmonella enterica serovar Typhimurium and Staphylococcus aureus in mice","volume":"71","author":"Lembo","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1189\/jlb.0113003","article-title":"TLR2 & Co: A critical analysis of the complex interactions between TLR2 and coreceptors","volume":"94","author":"Plantinga","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/nri2873","article-title":"Sterile inflammation: Sensing and reacting to damage","volume":"10","author":"Chen","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1128\/IAI.73.5.2940-2950.2005","article-title":"Differential induction of the toll-like receptor 4-MyD88-dependent and -independent signaling pathways by endotoxins","volume":"73","author":"Zughaier","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.molcel.2014.03.012","article-title":"A cross-disciplinary perspective on the innate immune responses to bacterial lipopolysaccharide","volume":"54","author":"Tan","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3947\/ic.2014.46.1.1","article-title":"Biomarkers of sepsis","volume":"46","author":"Cho","year":"2014","journal-title":"Infect. Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.cyto.2012.07.026","article-title":"Local and systemic occurrences of HMGB1 in gnotobiotic piglets infected with E. coli O55 are related to bacterial translocation and inflammatory cytokines","volume":"60","author":"Splichalova","year":"2012","journal-title":"Cytokine"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.cytogfr.2014.07.017","article-title":"IL-12-and IL-23 in health and disease","volume":"25","author":"Croxford","year":"2014","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1002\/eji.1830241026","article-title":"Differential expression of mRNA encoding interleukin-12 p35 and p40 subunits in situ","volume":"24","author":"Bette","year":"1994","journal-title":"Eur. J. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1365-3083.2008.02122.x","article-title":"New biomarkers in an acute model of live Escherichia coli-induced sepsis in pigs","volume":"68","author":"Castellheim","year":"2008","journal-title":"Scand. J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1111\/j.1462-5822.2006.00716.x","article-title":"Interferon signalling network in innate defence","volume":"8","author":"Takaoka","year":"2006","journal-title":"Cell Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev.iy.13.040195.001343","article-title":"Interleukin-12: A proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity","volume":"13","author":"Trinchieri","year":"1995","journal-title":"Annu. Rev. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cyto.2016.10.009","article-title":"Interferon-gamma in Salmonella pathogenesis: New tricks for an old dog","volume":"98","author":"Ingram","year":"2017","journal-title":"Cytokine"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10875-007-9126-7","article-title":"Pentraxins in innate immunity: From C-reactive protein to the long pentraxin PTX3","volume":"28","author":"Mantovani","year":"2008","journal-title":"J. Clin. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1128\/CMR.00016-12","article-title":"New approaches to sepsis: Molecular diagnostics and biomarkers","volume":"25","author":"Reinhart","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.cca.2016.07.002","article-title":"Diagnosing sepsis\u2014The role of laboratory medicine","volume":"460","author":"Fan","year":"2016","journal-title":"Clin. Chim. Acta"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/imm.13117","article-title":"Intestinal epithelial cells: At the interface of the microbiota and mucosal immunity","volume":"158","author":"Soderholm","year":"2019","journal-title":"Immunology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/food.19870310580","article-title":"The minipig as a model in gnotobiology","volume":"31","author":"Mandel","year":"1987","journal-title":"Nahrung"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. 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