Allelic Variation on Murine Chromosome 11 Modifies Host Inflammatory Responses and Resistance to

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Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36–74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.

Vyšlo v časopise: Allelic Variation on Murine Chromosome 11 Modifies Host Inflammatory Responses and Resistance to. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002469
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002469

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Zdroje

1. BrodskyIEMedzhitovR 2009 Targeting of immune signalling networks by bacterial pathogens. Nat Cell Biol 11 521 526

2. PitzschkeASchikoraAHirtH 2009 MAPK cascade signalling networks in plant defence. Curr Opin Plant Biol 12 421 426

3. BanksDJWardSCBradleyKA 2006 New insights into the functions of anthrax toxin. Expert Rev Mol Med 8 1 18

4. DangONavarroLAndersonKDavidM 2004 Cutting edge: anthrax lethal toxin inhibits activation of IFN-regulatory factor 3 by lipopolysaccharide. J Immunol 172 747 751

5. ErwinJLDaSilvaLMBavariSLittleSFFriedlanderAM 2001 Macrophage-derived cell lines do not express proinflammatory cytokines after exposure to Bacillus anthracis lethal toxin. Infect Immun 69 1175 1177

6. HsuLCParkJMZhangKLuoJLMaedaS 2004 The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428 341 345

7. ParkJMGretenFRLiZWKarinM 2002 Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science 297 2048 2051

8. PopovSGVillasmilRBernardiJGreneECardwellJ 2002 Effect of Bacillus anthracis lethal toxin on human peripheral blood mononuclear cells. FEBS Lett 527 211 215

9. HsuLCAliSRMcGillivraySTsengPHMariathasanS 2008 A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A 105 7803 7808

10. CuiXLiYLiXHaleyMMoayeriM 2006 Sublethal doses of Bacillus anthracis lethal toxin inhibit inflammation with lipopolysaccharide and Escherichia coli challenge but have opposite effects on survival. J Infect Dis 193 829 840

11. BergmanNHPassalacquaKDGaspardRShetron-RamaLMQuackenbushJ 2005 Murine macrophage transcriptional responses to Bacillus anthracis infection and intoxication. Infect Immun 73 1069 1080

12. LiuSMiller-RandolphSCrownDMoayeriMSastallaI 2010 Anthrax toxin targeting of myeloid cells through the CMG2 receptor is essential for establishment of Bacillus anthracis infections in mice. Cell Host Microbe 18 455 462

13. CoteCKDimezzoTLBanksDJFranceBBradleyKA 2008 Early interactions between fully virulent Bacillus anthracis and macrophages that influence the balance between spore clearance and development of a lethal infection. Microbes Infect 10 613 619

14. BoydenEDDietrichWF 2006 Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet 38 240 244

15. TerraJKCoteCKFranceBJenkinsALBozueJA 2010 Cutting edge: resistance to Bacillus anthracis infection mediated by a lethal toxin sensitive allele of Nalp1b/Nlrp1b. J Immunol 184 17 20

16. NyeSHWittenburgALEvansDLO'ConnorJARomanRJ 2007 Rat survival to anthrax lethal toxin is likely controlled by a single gene. Pharmacogenomics J 8 16 22

17. MoayeriMCrownDNewmanZLOkugawaSEckhausM 2010 Inflammasome sensor Nlrp1b-dependent resistance to anthrax is mediated by caspase-1, IL-1 signaling and neutrophil recruitment. PLoS Pathog 6 e1001222

18. LincolnREWalkerJSKleinFRosenwaldAJJonesWIJr 1967 Value of field data for extrapolation in anthrax. Fed Proc 26 1558 1562

19. WelkosSLKeenerTJGibbsPH 1986 Differences in susceptibility of inbred mice to Bacillus anthracis. Infect Immun 51 795 800

20. WelkosSLFriedlanderAM 1988 Pathogenesis and genetic control of resistance to the Sterne strain of Bacillus anthracis. Microb Pathog 4 53 69

21. WelkosSLTrotterRWBeckerDMNelsonGO 1989 Resistance to the Sterne strain of B. anthracis: phagocytic cell responses of resistant and susceptible mice. Microb Pathog 7 15 35

22. WelkosSLVietriNJGibbsPH 1993 Non-toxigenic derivatives of the Ames strain of Bacillus anthracis are fully virulent for mice: role of plasmid pX02 and chromosome in strain-dependent virulence. Microb Pathog 14 381 388

23. HarvillETLeeGGrippeVKMerkelTJ 2005 Complement depletion renders C57BL/6 mice sensitive to the Bacillus anthracis Sterne strain. Infect Immun 73 4420 4422

24. MoayeriMMartinezNWWigginsJYoungHALepplaSH 2004 Mouse susceptibility to anthrax lethal toxin is influenced by genetic factors in addition to those controlling macrophage sensitivity. Infect Immun 72 4439 4447

25. DavisRCJinARosalesMYuSXiaX 2007 A genome-wide set of congenic mouse strains derived from CAST/Ei on a C57BL/6 background. Genomics 90 306 313

26. RobertsJEWattersJWBallardJDDietrichWF 1998 Ltx1, a mouse locus that influences the susceptibility of macrophages to cytolysis caused by intoxication with Bacillus anthracis lethal factor, maps to chromosome 11. Mol Microbiol 29 581 591

27. ShikamaYKuroishiTNagaiYIwakuraYShimauchiH 2011 Muramyldipeptide augments the actions of lipopolysaccharide in mice by stimulating macrophages to produce pro-IL-1{beta} and by down-regulation of the suppressor of cytokine signaling 1 (SOCS1). Innate Immun 17 3 15

28. BiedermannTRockenM 2005 Pro- and anti-inflammatory effects of IL-4: from studies in mice to therapy of autoimmune diseases in humans. Ernst Schering Res Found Workshop 235 242

29. Adib-ConquyMCavaillonJM 2009 Compensatory anti-inflammatory response syndrome. Thromb Haemost 101 36 47

30. JonesJWKayagakiNBrozPHenryTNewtonK 2010 Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proc Natl Acad Sci U S A 107 9771 9776

31. HartPHVittiGFBurgessDRWhittyGAPiccoliDS 1989 Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2. Proc Natl Acad Sci U S A 86 3803 3807

32. VannierEMillerLCDinarelloCA 1992 Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist. Proc Natl Acad Sci U S A 89 4076 4080

33. CuiXMoayeriMLiYLiXHaleyM 2004 Lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats. Am J Physiol Regul Integr Comp Physiol 286 R699 709

34. TournierJNQuesnel-HellmannAMathieuJMontecuccoCTangWJ 2005 Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells. J Immunol 174 4934 4941

35. HughesMAGreenCSLowchyjLLeeGMGrippeVK 2005 MyD88-dependent signaling contributes to protection following Bacillus anthracis spore challenge of mice: implications for Toll-like receptor signaling. Infect Immun 73 7535 7540

36. KalnsJScruggsJMillenbaughNVivekanandaJShealyD 2002 TNF receptor 1, IL-1 receptor, and iNOS genetic knockout mice are not protected from anthrax infection. Biochem Biophys Res Commun 292 41 44

37. KangTJBasuSZhangLThomasKEVogelSN 2008 Bacillus anthracis spores and lethal toxin induce IL-1beta via functionally distinct signaling pathways. Eur J Immunol 38 1574 1584

38. OkugawaSMoayeriMEckhausMACrownDMiller-RandolphS 2011 MyD88-dependent signaling protects against anthrax lethal toxin-induced impairment of intestinal barrier function. Infect Immun 79 118 124

39. HenryTMonackDM 2007 Activation of the inflammasome upon Francisella tularensis infection: interplay of innate immune pathways and virulence factors. Cell Microbiol 9 2543 2551

40. DossSSchadtEEDrakeTALusisAJ 2005 Cis-acting expression quantitative trait loci in mice. Genome Res 15 681 691

41. SchadtEELambJYangXZhuJEdwardsS 2005 An integrative genomics approach to infer causal associations between gene expression and disease. Nat Genet 37 710 717

42. SchadtEEMonksSADrakeTALusisAJCheN 2003 Genetics of gene expression surveyed in maize, mouse and man. Nature 422 297 302

43. LanHRabagliaMEStoehrJPNadlerSTSchuelerKL 2003 Gene expression profiles of nondiabetic and diabetic obese mice suggest a role of hepatic lipogenic capacity in diabetes susceptibility. Diabetes 52 688 700

44. JansenRCNapJP 2001 Genetical genomics: the added value from segregation. Trends Genet 17 388 391

45. JansenRC 2003 Studying complex biological systems using multifactorial perturbation. Nat Rev Genet 4 145 151

46. McAllisterRDSinghYDu BoisWDPotterMBoehmT 2003 Susceptibility to anthrax lethal toxin is controlled by three linked quantitative trait Loci. Am J Pathol 163 1735 1741

47. WattersJWDietrichWF 2001 Genetic, physical, and transcript map of the Ltxs1 region of mouse chromosome 11. Genomics 73 223 231

48. HubnerNWallaceCAZimdahlHPetrettoESchulzH 2005 Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease. Nat Genet 37 243 253

49. SebastianiGOlienLGauthierSSkameneEMorganK 1998 Mapping of genetic modulators of natural resistance to infection with Salmonella typhimurium in wild-derived mice. Genomics 47 180 186

50. RaesGBrysLDahalBKBrandtJGrootenJ 2005 Macrophage galactose-type C-type lectins as novel markers for alternatively activated macrophages elicited by parasitic infections and allergic airway inflammation. J Leukoc Biol 77 321 327

51. SabaKDenda-NagaiKIrimuraT 2009 A C-type lectin MGL1/CD301a plays an anti-inflammatory role in murine experimental colitis. A J Pathol 174 144 152

52. GodsonCMitchellSHarveyKPetasisNAHoggN 2000 Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol 164 1663 1667

53. WangYTangYTengLWuYZhaoX 2006 Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol 7 139 147

54. FanHBittoAZingarelliBLuttrellLMBorgK 2010 Beta-arrestin 2 negatively regulates sepsis-induced inflammation. Immunology 130 344 351

55. PorterKJGonipetaBParvataneniSAppledornDMPatialS 2010 Regulation of lipopolysaccharide-induced inflammatory response and endotoxemia by beta-arrestins. J Cell Physiol 225 406 416

56. TadagavadiRKWangWRameshG 2010 Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. J Immunol 185 3750 3758

57. UzaNNakaseHYamamotoSYoshinoTTakedaY 2011 SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation. Gut 60 1494 1505

58. LuJPierceMFranklinAJillingTStafforiniDM 2010 Dual roles of endogenous platelet-activating factor acetylhydrolase in a murine model of necrotizing enterocolitis. Pediatr Res 68 225 230

59. IvakineEAGulbanOMMortin-TothSMWankiewiczEScottC 2006 Molecular genetic analysis of the Idd4 locus implicates the IFN response in type 1 diabetes susceptibility in nonobese diabetic mice. J Immunol 176 2976 2990

60. Sancho-ShimizuVKhanRMostowySLariviereLWilkinsonR 2007 Molecular genetic analysis of two loci (Ity2 and Ity3) involved in the host response to infection with Salmonella typhimurium using congenic mice and expression profiling. Genetics 177 1125 1139

61. AliSRTimmerAMBilgramiSParkEJEckmannL 2011 Anthrax toxin induces macrophage death by p38 MAPK inhibition but leads to inflammasome activation via ATP leakage. Immunity 35 34 44

62. FranchiLEigenbrodTMunoz-PlanilloRNunezG 2009 The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 10 241 247

63. CastellheimABrekkeOLEspevikTHarboeMMollnesTE 2009 Innate immune responses to danger signals in systemic inflammatory response syndrome and sepsis. Scand J Immunol 69 479 491

64. TakahashiHTsudaYKobayashiMHerndonDNSuzukiF 2006 CCL2 as a trigger of manifestations of compensatory anti-inflammatory response syndrome in mice with severe systemic inflammatory response syndrome. J Leukoc Biol 79 789 796

65. KlempnerMSTalbotEALeeSIZakiSFerraroMJ 2010 Case records of the Massachusetts General Hospital. Case 25-2010. A 24-year-old woman with abdominal pain and shock. N Engl J Med 363 766 777

66. TorreDTambiniRAristodemoSGavazzeniGGoglioA 2000 Anti-inflammatory response of IL-4, IL-10 and TGF-beta in patients with systemic inflammatory response syndrome. Mediators Inflamm 9 193 195

67. PeyssonnauxCCejudo-MartinPDoedensAZinkernagelASJohnsonRS 2007 Cutting edge: Essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide-induced sepsis. J Immunol 178 7516 7519

68. AyalaAChungCSGrutkoskiPSSongGY 2003 Mechanisms of immune resolution. Crit Care Med 31 S558 571

69. MartinonF 2010 Update on biology: uric acid and the activation of immune and inflammatory cells. Curr Rheumatol Rep 12 135 141

70. ParkSLepplaSH 2000 Optimized production and purification of Bacillus anthracis lethal factor. Protein Expr Purif 18 293 302

71. GuptaPKMoayeriMCrownDFattahRJLepplaSH 2008 Role of N-terminal amino acids in the potency of anthrax lethal factor. PLoS One 3 e3130

72. AveretteKMPrattMRYangYBassilianSWhiteleggeJP 2009 Anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release is Nlrp1b/Nalp1b-dependent. PLoS ONE 4 e7913

73. SchadtEEMolonyCChudinEHaoKYangX 2008 Mapping the genetic architecture of gene expression in human liver. PLoS Biol 6 e107