Toll-Like Receptor 4 Signaling in the Ileum and Colon of Gnotobiotic Piglets Infected with Salmonella Typhimurium or Its Isogenic ∆rfa Mutants

. 2020 Aug 23 ; 12 (9) : . [epub] 20200823

Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid32842482

Grantová podpora
COST LD15090 Ministerstvo Školství, Mládeže a Tělovýchovy - International
Institutional Research Concept RVO 61388971 Mikrobiologický ústav AV ČR - International
CZ.02.1.01/0.0/0.0/16_025/0007404 Ministerstvo Školství, Mládeže a Tělovýchovy - International

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 ∆rfa 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 ∆rfa mutants were related to the completeness of their LPS chain. The transcription of IL-12/23 p40, IFN-γ, and IL-6 in the intestine and the intestinal and plasmatic levels of IL-12/23 p40 and IL-6 but not IFN-γ were related to the activation of TLR2 and TLR4 signaling pathways. The avirulent S. Typhimurium ∆rfa 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.

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Raetz C.R., Whitfield C. Lipopolysaccharide endotoxins. Annu. Rev. Biochem. 2002;71:635–700. doi: 10.1146/annurev.biochem.71.110601.135414. PubMed DOI PMC

Caroff M., Karibian D. Structure of bacterial lipopolysaccharides. Carbohydr. Res. 2003;338:2431–2447. doi: 10.1016/j.carres.2003.07.010. PubMed DOI

Hitchcock P.J., Leive L., Makela P.H., Rietschel E.T., Strittmatter W., Morrison D.C. Lipopolysaccharide nomenclature--past, present, and future. J. Bacteriol. 1986;166:699–705. doi: 10.1128/JB.166.3.699-705.1986. PubMed DOI PMC

Molinaro A., Holst O., Di L.F., Callaghan M., Nurisso A., D′Errico G., Zamyatina A., Peri F., Berisio R., Jerala R., et al. Chemistry of lipid A: At the heart of innate immunity. Chemistry. 2015;21:500–519. doi: 10.1002/chem.201403923. PubMed DOI

Rietschel E.T., Brade H., Brade L., Brandenburg K., Schade U., Seydel U., Zahringer U., Galanos C., Luderitz O., Westphal O. Lipid A, the endotoxic center of bacterial lipopolysaccharides: Relation of chemical structure to biological activity. Prog. Clin. Biol. Res. 1987;231:25–53. doi: 10.1007/BF01716559. PubMed DOI

Freudenberg M.A., Tchaptchet S., Keck S., Fejer G., Huber M., Schutze N., Beutler B., Galanos C. Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections: Benefits and hazards of LPS hypersensitivity. Immunobiology. 2008;213:193–203. doi: 10.1016/j.imbio.2007.11.008. PubMed DOI

Huber M., Kalis C., Keck S., Jiang Z., Georgel P., Du X., Shamel L., Sovath S., Mudd S., Beutler B., et al. R-form LPS, the master key to the activation ofTLR4/MD-2-positive cells. Eur. J. Immunol. 2006;36:701–711. doi: 10.1002/eji.200535593. PubMed DOI

Nikaido H. Prevention of drug access to bacterial targets: Permeability barriers and active efflux. Science. 1994;264:382–388. doi: 10.1126/science.8153625. PubMed DOI

Beveridge T.J. Structures of gram-negative cell walls and their derived membrane vesicles. J. Bacteriol. 1999;181:4725–4733. doi: 10.1128/JB.181.16.4725-4733.1999. PubMed DOI PMC

Cinel I., Opal S.M. Molecular biology of inflammation and sepsis: A primer. Crit. Care Med. 2009;37:291–304. doi: 10.1097/CCM.0b013e31819267fb. PubMed DOI

Cohen J. The immunopathogenesis of sepsis. Nature. 2002;420:885–891. doi: 10.1038/nature01326. PubMed DOI

Beutler B., Hoebe K., Du X., Ulevitch R.J. How we detect microbes and respond to them: The Toll-like receptors and their transducers. J. Leukoc. Biol. 2003;74:479–485. doi: 10.1189/jlb.0203082. PubMed DOI

Freudenberg M.A., Merlin T., Gumenscheimer M., Kalis C., Landmann R., Galanos C. Role of lipopolysaccharide susceptibility in the innate immune response to Salmonella typhimurium infection: LPS, a primary target for recognition of Gram-negative bacteria. Microbes Infect. 2001;3:1213–1222. doi: 10.1016/S1286-4579(01)01481-2. PubMed DOI

Cavaillon J.M. Exotoxins and endotoxins: Inducers of inflammatory cytokines. Toxicon. 2018;149:45–53. doi: 10.1016/j.toxicon.2017.10.016. PubMed DOI

Cavaillon J.M., Singer M., Skirecki T. Sepsis therapies: Learning from 30 years of failure of translational research to propose new leads. EMBO Mol. Med. 2020;12:e10128. doi: 10.15252/emmm.201810128. PubMed DOI PMC

Mehta S., Gill S.E. Improving clinical outcomes in sepsis and multiple organ dysfunction through precision medicine. J. Thorac. Dis. 2019;11:21–28. doi: 10.21037/jtd.2018.11.74. PubMed DOI PMC

Liu D., Cao S., Zhou Y., Xiong Y. Recent advances in endotoxin tolerance. J. Cell Biochem. 2019;120:56–70. doi: 10.1002/jcb.27547. PubMed DOI

Ryu J.K., Kim S.J., Rah S.H., Kang J.I., Jung H.E., Lee D., Lee H.K., Lee J.O., Park B.S., Yoon T.Y., et al. Reconstruction of LPS transfer cascade reveals structural determinants within LBP, CD14, and TLR4-MD2 for efficient LPS recognition and transfer. Immunity. 2017;46:38–50. doi: 10.1016/j.immuni.2016.11.007. PubMed DOI

Kagan J.C. Lipopolysaccharide detection across the kingdoms of life. Trends Immunol. 2017;38:696–704. doi: 10.1016/j.it.2017.05.001. PubMed DOI PMC

Oswald I.P. Role of intestinal epithelial cells in the innate immune defence of the pig intestine. Vet. Res. 2006;37:359–368. doi: 10.1051/vetres:2006006. PubMed DOI

Heine H., Rietschel E.T., Ulmer A.J. The biology of endotoxin. Mol. Biotechnol. 2001;19:279–296. doi: 10.1385/MB:19:3:279. PubMed DOI

Kawai T., Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34:637–650. doi: 10.1016/j.immuni.2011.05.006. PubMed DOI

Cao X. Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat. Rev. Immunol. 2016;16:35–50. doi: 10.1038/nri.2015.8. PubMed DOI

Park B.S., Lee J.O. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp. Mol. Med. 2013;45:e66. doi: 10.1038/emm.2013.97. PubMed DOI PMC

Raby A.C., Holst B., Le B.E., Diaz C., Ferran E., Conraux L., Guillemot J.C., Coles B., Kift-Morgan A., Colmont C.S., et al. Targeting the TLR co-receptor CD14 with TLR2-derived peptides modulates immune responses to pathogens. Sci. Transl. Med. 2013;5:185ra64. doi: 10.1126/scitranslmed.3005544. PubMed DOI

Baumann C.L., Aspalter I.M., Sharif O., Pichlmair A., Bluml S., Grebien F., Bruckner M., Pasierbek P., Aumayr K., Planyavsky M., et al. CD14 is a coreceptor of Toll-like receptors 7 and 9. J. Exp. Med. 2010;207:2689–2701. doi: 10.1084/jem.20101111. PubMed DOI PMC

Osuchowski M.F., Ayala A., Bahrami S., Bauer M., Boros M., Cavaillon J.M., Chaudry I.H., Coopersmith C.M., Deutschman C., Drechsler S., et al. Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): An international expert consensus initiative for improvement of animal modeling in sepsis. Infection. 2018;46:687–691. doi: 10.1007/s15010-018-1183-8. PubMed DOI PMC

Bassols A., Costa C., Eckersall P.D., Osada J., Sabria J., Tibau J. The pig as an animal model for human pathologies: A proteomics perspective. Proteom. Clin. Appl. 2014;8:715–731. doi: 10.1002/prca.201300099. PubMed DOI

Xiao L., Estelle J., Kiilerich P., Ramayo-Caldas Y., Xia Z., Feng Q., Liang S., Pedersen A.O., Kjeldsen N.J., Liu C., et al. A reference gene catalogue of the pig gut microbiome. Nat. Microbiol. 2016;1:16161. doi: 10.1038/nmicrobiol.2016.161. PubMed DOI

Burrin D., Sangild P.T., Stoll B., Thymann T., Buddington R., Marini J., Olutoye O., Shulman R.J. Translational Advances in Pediatric Nutrition and Gastroenterology: New Insights from Pig Models. Annu. Rev. Anim Biosci. 2020;8:321–354. doi: 10.1146/annurev-animal-020518-115142. PubMed DOI

Meurens F., Summerfield A., Nauwynck H., Saif L., Gerdts V. The pig: A model for human infectious diseases. Trends Microbiol. 2012;20:50–57. doi: 10.1016/j.tim.2011.11.002. PubMed DOI PMC

Waterhouse A., Leslie D.C., Bolgen D.E., Lightbown S., Dimitrakakis N., Cartwright M.J., Seiler B., Lightbown K., Smith K., Lombardo P., et al. Modified Clinical Monitoring Assesment Criteria for Multi-Organ Failure during Bacteremia and Sepsis Progression in a Pig Model. [(accessed on 16 August 2020)];Adv. Crit. Care Med. 2018 1:2. Available online: http://www.scientificoajournals.org/pdf/ccm.1002.pdf.

Hurley D., McCusker M.P., Fanning S., Martins M. Salmonella-host interactions-modulation of the host innate immune system. Front. Immunol. 2014;5:481. doi: 10.3389/fimmu.2014.00481. PubMed DOI PMC

Campos J., Mourao J., Peixe L., Antunes P. Non-typhoidal Salmonella in the pig production chain: A comprehensive analysis of Its impact on human health. Pathogens. 2019;8:19. doi: 10.3390/pathogens8010019. PubMed DOI PMC

Kaiser P., Hardt W.D. Salmonella typhimurium diarrhea: Switching the mucosal epithelium from homeostasis to defense. Curr. Opin. Immunol. 2011;23:456–463. doi: 10.1016/j.coi.2011.06.004. PubMed DOI

Barthel M., Hapfelmeier S., Quintanilla-Martinez L., Kremer M., Rohde M., Hogardt M., Pfeffer K., Russmann H., Hardt W.D. Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect. Immun. 2003;71:2839–2858. doi: 10.1128/IAI.71.5.2839-2858.2003. PubMed DOI PMC

Zhang S., Kingsley R.A., Santos R.L., Andrews-Polymenis H., Raffatellu M., Figueiredo J., Nunes J., Tsolis R.M., Adams L.G., Baumler A.J. Molecular pathogenesis of Salmonella enterica serotype typhimurium-induced diarrhea. Infect. Immun. 2003;71:1–12. doi: 10.1128/IAI.71.1.1-12.2003. PubMed DOI PMC

Wen S.C., Best E., Nourse C. Non-typhoidal Salmonella infections in children: Review of literature and recommendations for management. J. Paediatr. Child. Health. 2017;53:936–941. doi: 10.1111/jpc.13585. PubMed DOI

Rai B., Utekar T., Ray R. Preterm delivery and neonatal meningitis due to transplacental acquisition of non-typhoidal Salmonella serovar montevideo. BMJ Case. Rep. 2014;2014 doi: 10.1136/bcr-2014-205082. PubMed DOI PMC

Mooser C., Gomez de A.M., Ganal-Vonarburg S.C. Standardization in host-microbiota interaction studies: Challenges, gnotobiology as a tool, and perspective. Curr. Opin. Microbiol. 2018;44:50–60. doi: 10.1016/j.mib.2018.07.007. PubMed DOI

Ducarmon Q.R., Zwittink R.D., Hornung B.V.H., van S.W., Young V.B., Kuijper E.J. Gut icrobiota and Colonization Resistance against Bacterial Enteric Infection. Microbiol. Mol. Biol. Rev. 2019;83 doi: 10.1128/MMBR.00007-19. PubMed DOI PMC

Splichalova A., Splichal I., Chmelarova P., Trebichavsky I. Alarmin HMGB1 is released in the small intestine of gnotobiotic piglets infected with enteric pathogens and its level in plasma reflects severity of sepsis. J. Clin. Immunol. 2011;31:488–497. doi: 10.1007/s10875-010-9505-3. PubMed DOI

Splichalova A., Trebichavsky I., Rada V., Vlkova E., Sonnenborn U., Splichal I. Interference of Bifidobacterium choerinum or Escherichia coli Nissle 1917 with Salmonella Typhimurium in gnotobiotic piglets correlates with cytokine patterns in blood and intestine. Clin. Exp. Immunol. 2011;163:242–249. doi: 10.1111/j.1365-2249.2010.04283.x. PubMed DOI PMC

Foster N., Lovell M.A., Marston K.L., Hulme S.D., Frost A.J., Bland P., Barrow P.A. Rapid protection of gnotobiotic pigs against experimental salmonellosis following induction of polymorphonuclear leukocytes by avirulent Salmonella enterica. Infect. Immun. 2003;71:2182–2191. doi: 10.1128/IAI.71.4.2182-2191.2003. PubMed DOI PMC

Splichalova A., Slavikova V., Splichalova Z., Splichal I. Preterm life in sterile conditions: A study on preterm, germ-free piglets. Front. Immunol. 2018;9:220. doi: 10.3389/fimmu.2018.00220. PubMed DOI PMC

Basic M., Bleich A. Gnotobiotics: Past, present and future. Lab. Anim. 2019;53:232–243. doi: 10.1177/0023677219836715. PubMed DOI

Salmon H., Berri M., Gerdts V., Meurens F. Humoral and cellular factors of maternal immunity in swine. Dev. Comp. Immunol. 2009;33:384–393. doi: 10.1016/j.dci.2008.07.007. PubMed DOI

Roberts R.M., Green J.A., Schulz L.C. The evolution of the placenta. Reproduction. 2016;152:R179–R189. doi: 10.1530/REP-16-0325. PubMed DOI PMC

Galen J.E., Buskirk A.D., Tennant S.M., Pasetti M.F. Live attenuated human Salmonella vaccine candidates: Tracking the pathogen in natural infection and stimulation of host immunity. Ecosal. Plus. 2016:7. doi: 10.1128/ecosalplus.ESP-0010-2016. PubMed DOI PMC

Kong Q., Yang J., Liu Q., Alamuri P., Roland K.L., Curtiss R. III Effect of deletion of genes involved in lipopolysaccharide core and O-antigen synthesis on virulence and immunogenicity of Salmonella enterica serovar Typhimurium. Infect. Immun. 2011;79:4227–4239. doi: 10.1128/IAI.05398-11. PubMed DOI PMC

Chang Y.F., Hou J.N., Lin H.H., Wu C.P., Chu C. Differences in immune responses of pigs vaccinated with Salmonella Typhimurium and S. Choleraesuis strains and challenged with S. Choleraesuis. Comp. Immunol. Microbiol. Infect. Dis. 2019;65:41–47. doi: 10.1016/j.cimid.2019.04.003. PubMed DOI

Iwasaki A., Medzhitov R. Control of adaptive immunity by the innate immune system. Nat. Immunol. 2015;16:343–353. doi: 10.1038/ni.3123. PubMed DOI PMC

McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P., Courtney L., Porwollik S., Ali J., Dante M., Du F., et al. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature. 2001;413:852–856. doi: 10.1038/35101614. PubMed DOI

Clarke R.C., Gyles C.L. Virulence of wild and mutant strains of Salmonella typhimurium in ligated intestinal segments of calves, pigs, and rabbits. Am. J. Vet. Res. 1987;48:504–510. PubMed

Trebichavsky I., Dlabac V., Rehakova Z., Zahradnickova M., Splichal I. Cellular changes and cytokine expression in the ilea of gnotobiotic piglets resulting from peroral Salmonella typhimurium challenge. Infect. Immun. 1997;65:5244–5249. doi: 10.1128/IAI.65.12.5244-5249.1997. PubMed DOI PMC

Splichal I., Rychlik I., Gregorova D., Sebkova A., Trebichavsky I., Splichalova A., Muneta Y., Mori Y. Susceptibility of germ-free pigs to challenge with protease mutants of Salmonella enterica serovar Typhimurium. Immunobiology. 2007;212:577–582. doi: 10.1016/j.imbio.2007.05.001. PubMed DOI

Trebichavsky I., Splichalova A., Rychlik I., Hojna H., Muneta Y., Mori Y., Splichal I. Attenuated aroA Salmonella enterica serovar Typhimurium does not induce inflammatory response and early protection of gnotobiotic pigs against parental virulent LT2 strain. Vaccine. 2006;24:4285–4289. doi: 10.1016/j.vaccine.2006.02.054. PubMed DOI

Goldfarb R.D., Dellinger R.P., Parrillo J.E. Porcine models of severe sepsis: Emphasis on porcine peritonitis. Shock. 2005;24(Suppl. 1):75–81. doi: 10.1097/01.shk.0000191337.01036.b7. PubMed DOI

Fink M.P. Animal models of sepsis. Virulence. 2014;5:143–153. doi: 10.4161/viru.26083. PubMed DOI PMC

Pierrakos C., Vincent J.L. Sepsis biomarkers: A review. Crit. Care. 2010;14:R15. doi: 10.1186/cc8872. PubMed DOI PMC

Galanos C., Freudenberg M.A. Mechanisms of endotoxin shock and endotoxin hypersensitivity. Immunobiology. 1993;187:346–356. doi: 10.1016/S0171-2985(11)80349-9. PubMed DOI

Splichal I., Trebichavsky I., Splichalova A., Barrow P.A. 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. Vet. Immunol. Immunopathol. 2005;103:155–161. doi: 10.1016/j.vetimm.2004.09.001. PubMed DOI

Splichal I., Donovan S.M., Jenistova V., Splichalova I., Salmonova H., Vlkova E., Neuzil B.V., Sinkora M., Killer J., Skrivanova E., et al. 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. 2019;20:6294. doi: 10.3390/ijms20246294. PubMed DOI PMC

Splichalova A., Splichalova Z., Karasova D., Rychlik I., Trevisi P., Sinkora M., Splichal I. Impact of the lipopolysaccharide chemotype of Salmonella enterica serovar Typhimurium on virulence in gnotobiotic piglets. Toxins. 2019;11:534. doi: 10.3390/toxins11090534. PubMed DOI PMC

Awoniyi M., Miller S.I., Wilson C.B., Hajjar A.M., Smith K.D. Homeostatic regulation of Salmonella-induced mucosal inflammation and injury by IL-23. PLoS. ONE. 2012;7:e37311. doi: 10.1371/journal.pone.0037311. PubMed DOI PMC

Kak G., Raza M., Tiwari B.K. Interferon-gamma (IFN-gamma): Exploring its implications in infectious diseases. Biomol. Concepts. 2018;9:64–79. doi: 10.1515/bmc-2018-0007. PubMed DOI

Song J., Park D.W., Moon S., Cho H.J., Park J.H., Seok H., Choi W.S. 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. 2019;19:968. doi: 10.1186/s12879-019-4618-7. PubMed DOI PMC

Splichal I., Splichalova A. Experimental Enteric Bacterial Infections in Pigs. J. Infect. Dis. 2018;218:504–505. doi: 10.1093/infdis/jiy185. PubMed DOI

Thorgersen E.B., Hellerud B.C., Nielsen E.W., Barratt-Due A., Fure H., Lindstad J.K., Pharo A., Fosse E., Tonnessen T.I., Johansen H.T., et al. CD14 inhibition efficiently attenuates early inflammatory and hemostatic responses in Escherichia coli sepsis in pigs. FASEB J. 2010;24:712–722. doi: 10.1096/fj.09-140798. PubMed DOI PMC

Burkey T.E., Skjolaas K.A., Dritz S.S., Minton J.E. 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. Vet. Immunol. Immunopathol. 2007;115:309–319. doi: 10.1016/j.vetimm.2006.11.012. PubMed DOI

Burkey T.E., Skjolaas K.A., Dritz S.S., Minton J.E. Expression of porcine Toll-like receptor 2, 4 and 9 gene transcripts in the presence of lipopolysaccharide and Salmonella enterica serovars Typhimurium and Choleraesuis. Vet. Immunol. Immunopathol. 2009;130:96–101. doi: 10.1016/j.vetimm.2008.12.027. PubMed DOI

Collado-Romero M., Arce C., Ramirez-Boo M., Carvajal A., Garrido J.J. Quantitative analysis of the immune response upon Salmonella typhimurium infection along the porcine intestinal gut. Vet. Res. 2010;41:23. doi: 10.1051/vetres/2009072. PubMed DOI PMC

Vaure C., Liu Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front. Immunol. 2014;5:316. doi: 10.3389/fimmu.2014.00316. PubMed DOI PMC

Vogt S.L., Pena-Diaz J., Finlay B.B. Chemical communication in the gut: Effects of microbiota-generated metabolites on gastrointestinal bacterial pathogens. Anaerobe. 2015;34:106–115. doi: 10.1016/j.anaerobe.2015.05.002. PubMed DOI

Dziarski R., Wang Q., Miyake K., Kirschning C.J., Gupta D. 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. J. Immunol. 2001;166:1938–1944. doi: 10.4049/jimmunol.166.3.1938. PubMed DOI

Lembo A., Kalis C., Kirschning C.J., Mitolo V., Jirillo E., Wagner H., Galanos C., Freudenberg M.A. Differential contribution of Toll-like receptors 4 and 2 to the cytokine response to Salmonella enterica serovar Typhimurium and Staphylococcus aureus in mice. Infect. Immun. 2003;71:6058–6062. doi: 10.1128/IAI.71.10.6058-6062.2003. PubMed DOI PMC

Van Bergenhenegouwen J., Plantinga T.S., Joosten L.A., Netea M.G., Folkerts G., Kraneveld A.D., Garssen J., Vos A.P. TLR2 & Co: A critical analysis of the complex interactions between TLR2 and coreceptors. J. Leukoc. Biol. 2013;94:885–902. doi: 10.1189/jlb.0113003. PubMed DOI

Chen G.Y., Nunez G. Sterile inflammation: Sensing and reacting to damage. Nat. Rev. Immunol. 2010;10:826–837. doi: 10.1038/nri2873. PubMed DOI PMC

Zughaier S.M., Zimmer S.M., Datta A., Carlson R.W., Stephens D.S. Differential induction of the toll-like receptor 4-MyD88-dependent and -independent signaling pathways by endotoxins. Infect. Immun. 2005;73:2940–2950. doi: 10.1128/IAI.73.5.2940-2950.2005. PubMed DOI PMC

Tan Y., Kagan J.C. A cross-disciplinary perspective on the innate immune responses to bacterial lipopolysaccharide. Mol. Cell. 2014;54:212–223. doi: 10.1016/j.molcel.2014.03.012. PubMed DOI PMC

Cho S.Y., Choi J.H. Biomarkers of sepsis. Infect. Chemother. 2014;46:1–12. doi: 10.3947/ic.2014.46.1.1. PubMed DOI PMC

Splichalova A., Splichal I. Local and systemic occurrences of HMGB1 in gnotobiotic piglets infected with E. coli O55 are related to bacterial translocation and inflammatory cytokines. Cytokine. 2012;60:597–600. doi: 10.1016/j.cyto.2012.07.026. PubMed DOI

Croxford A.L., Kulig P., Becher B. IL-12-and IL-23 in health and disease. Cytokine Growth Factor Rev. 2014;25:415–421. doi: 10.1016/j.cytogfr.2014.07.017. PubMed DOI

Bette M., Jin S.C., Germann T., Schafer M.K., Weihe E., Rude E., Fleischer B. Differential expression of mRNA encoding interleukin-12 p35 and p40 subunits in situ. Eur. J. Immunol. 1994;24:2435–2440. doi: 10.1002/eji.1830241026. PubMed DOI

Castellheim A., Thorgersen E.B., Hellerud B.C., Pharo A., Johansen H.T., Brosstad F., Gaustad P., Brun H., Fosse E., Tonnessen T.I., et al. New biomarkers in an acute model of live Escherichia coli-induced sepsis in pigs. Scand. J. Immunol. 2008;68:75–84. doi: 10.1111/j.1365-3083.2008.02122.x. PubMed DOI

Takaoka A., Yanai H. Interferon signalling network in innate defence. Cell Microbiol. 2006;8:907–922. doi: 10.1111/j.1462-5822.2006.00716.x. PubMed DOI

Trinchieri G. Interleukin-12: A proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu. Rev. Immunol. 1995;13:251–276. doi: 10.1146/annurev.iy.13.040195.001343. PubMed DOI

Ingram J.P., Brodsky I.E., Balachandran S. Interferon-gamma in Salmonella pathogenesis: New tricks for an old dog. Cytokine. 2017;98:27–32. doi: 10.1016/j.cyto.2016.10.009. PubMed DOI PMC

Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.D., Coopersmith C.M., et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA. 2016;315:801–810. doi: 10.1001/jama.2016.0287. PubMed DOI PMC

Mantovani A., Garlanda C., Doni A., Bottazzi B. Pentraxins in innate immunity: From C-reactive protein to the long pentraxin PTX3. J. Clin. Immunol. 2008;28:1–13. doi: 10.1007/s10875-007-9126-7. PubMed DOI

Reinhart K., Bauer M., Riedemann N.C., Hartog C.S. New approaches to sepsis: Molecular diagnostics and biomarkers. Clin. Microbiol. Rev. 2012;25:609–634. doi: 10.1128/CMR.00016-12. PubMed DOI PMC

Fan S.L., Miller N.S., Lee J., Remick D.G. Diagnosing sepsis—The role of laboratory medicine. Clin. Chim. Acta. 2016;460:203–210. doi: 10.1016/j.cca.2016.07.002. PubMed DOI PMC

Soderholm A.T., Pedicord V.A. Intestinal epithelial cells: At the interface of the microbiota and mucosal immunity. Immunology. 2019;158:267–280. doi: 10.1111/imm.13117. PubMed DOI PMC

Mandel L., Travnicek J. The minipig as a model in gnotobiology. Nahrung. 1987;31:613–618. doi: 10.1002/food.19870310580. PubMed DOI

Schmittgen T.D., Livak K.J. Analyzing real-time PCR data by the comparative C(T) method. Nat. Protoc. 2008;3:1101–1108. doi: 10.1038/nprot.2008.73. PubMed DOI

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