and Are Associated with Murine Susceptibility to Infection and Human Sepsis

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Staphylococcus aureus causes life-threatening infections in humans. Host genetic determinants influence the outcome of S. aureus infection, yet are poorly understood. Susceptible A/J and resistant C57BL/6J mice provide a unique platform to study the genetic difference responsible for variable host response to S. aureus infection. We showed that chromosome 11 in A/J was responsible for susceptibility to S. aureus. We further identified a QTL locus on Chromosome 11 significantly associated with S. aureus susceptibility. Five genes in the QTL (Dcaf7, Dusp3, Fam134c, Psme3, and Slc4a1) were significantly differently expressed in a) susceptible vs. resistant mice, and b) humans with S. aureus blood stream infection vs. healthy human subjects. Three genes (Dusp3, Psme3, and Dcaf7) were down-regulated in susceptible A/J mice. siRNA-mediated knockdown of Dusp3 and Psme3 in bone marrow derived macrophage (BMDMs) significantly enhanced cytokine responses through NF-κB activity upon S. aureus challenge in a pattern that was also present in S. aureus-challenged BMDMs from susceptible CSS11 (chr. 11 from A/J but otherwise C57BL/6J) mice, but not resistant C57BL/6J mice. These findings suggest that Dusp3 and Psme3 contribute to S. aureus infection susceptibility in A/J mice and play a role in human S. aureus infection.

Vyšlo v časopise: and Are Associated with Murine Susceptibility to Infection and Human Sepsis. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004149
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004149

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Zdroje

1. BayerAS (1982) Staphylococcal bacteremia and endocarditis: state of the art. Arch Intern Med 142: 1169–1177.

2. EadyEA, CoveJH (2003) Staphylococcal resistance revisited: community-acquired methicillin resistant Staphylococcus aureus–an emerging problem for the management of skin and soft tissue infections. Curr Opin Infect Dis 16: 103–124.

3. MarchantB, BrownJ (1987) Toxic shock syndrome and staphylococcal pneumonia. Lancet 2: 578.

4. VerhoefJ, VerbrughHA (1981) Host determinants in staphylococcal disease. Annu Rev Med 32: 107–122.

5. von Kockritz-BlickwedeM, RohdeM, OehmckeS, MillerLS, CheungAL, et al. (2008) Immunological mechanisms underlying the genetic predisposition to severe Staphylococcus aureus infection in the mouse model. Am J Pathol 173: 1657–1668.

6. SongZ, SongY, YinJ, ShenY, YaoC, et al. (2012) Genetic variation in the TNF gene is associated with susceptibility to severe sepsis, but not with mortality. PLoS One 7: e46113.

7. SongZ, YaoC, YinJ, TongC, ZhuD, et al. (2012) Genetic variation in the TNF receptor-associated factor 6 gene is associated with susceptibility to sepsis-induced acute lung injury. J Transl Med 10: 166.

8. AdrianiKS, BrouwerMC, BaasF, ZwindermanAH, van der EndeA, et al. (2012) Genetic variation in the beta2-adrenocepter gene is associated with susceptibility to bacterial meningitis in adults. PLoS One 7: e37618.

9. NeteaMG, WijmengaC, O'NeillLA (2012) Genetic variation in Toll-like receptors and disease susceptibility. Nat Immunol 13: 535–542.

10. NakadaTA, RussellJA, BoydJH, WalleyKR (2011) IL17A genetic variation is associated with altered susceptibility to Gram-positive infection and mortality of severe sepsis. Crit Care 15: R254.

11. AhnSH, DeshmukhH, JohnsonN, CowellLG, RudeTH, et al. (2010) Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses. PLoS Pathog 6: e1001088.

12. JohnsonNV, AhnSH, DeshmukhH, LevinMK, NelsonCL, et al. (2012) Haplotype Association Mapping Identifies a Candidate Gene Region in Mice Infected With Staphylococcus aureus. G3 (Bethesda) 2: 693–700.

13. SugiN, WhistonEA, KsanderBR, GregoryMS (2013) Increased resistance to Staphylococcus aureus endophthalmitis in BALB/c mice: Fas ligand is required for resolution of inflammation but not for bacterial clearance. Infect Immun 81: 2217–2225.

14. SeokJ, WarrenHS, CuencaAG, MindrinosMN, BakerHV, et al. (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 110: 3507–3512.

15. YanQ, CarmodyRJ, QuZ, RuanQ, JagerJ, et al. (2012) Nuclear factor-kappaB binding motifs specify Toll-like receptor-induced gene repression through an inducible repressosome. Proc Natl Acad Sci U S A 109: 14140–14145.

16. KarraschT, KimJS, MuhlbauerM, MagnessST, JobinC (2007) Gnotobiotic IL-10−/−;NF-kappa B(EGFP) mice reveal the critical role of TLR/NF-kappa B signaling in commensal bacteria-induced colitis. J Immunol 178: 6522–6532.

17. Hedengren-OlcottM, OlcottMC, MooneyDT, EkengrenS, GellerBL, et al. (2004) Differential activation of the NF-kappaB-like factors Relish and Dif in Drosophila melanogaster by fungi and Gram-positive bacteria. J Biol Chem 279: 21121–21127.

18. MitchellG, GrondinG, BilodeauG, CantinAM, MalouinF (2011) Infection of polarized airway epithelial cells by normal and small-colony variant strains of Staphylococcus aureus is increased in cells with abnormal cystic fibrosis transmembrane conductance regulator function and is influenced by NF-kappaB. Infect Immun 79: 3541–3551.

19. GjertssonI, HultgrenOH, CollinsLV, PetterssonS, TarkowskiA (2001) Impact of transcription factors AP-1 and NF-kappaB on the outcome of experimental Staphylococcus aureus arthritis and sepsis. Microbes Infect 3: 527–534.

20. PoundP, EbrahimS, SandercockP, BrackenMB, RobertsI, et al. (2004) Where is the evidence that animal research benefits humans? BMJ 328: 514–517.

21. HackamDG, RedelmeierDA (2006) Translation of research evidence from animals to humans. JAMA 296: 1731–1732.

22. van der WorpHB, HowellsDW, SenaES, PorrittMJ, RewellS, et al. (2010) Can animal models of disease reliably inform human studies? PLoS Med 7: e1000245.

23. RiceJ (2012) Animal models: Not close enough. Nature 484: S9.

24. BaltimoreD (2011) NF-kappaB is 25. Nat Immunol 12: 683–685.

25. KarinM (2009) NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol 1: a000141.

26. ArimuraY, YagiJ (2010) Comprehensive expression profiles of genes for protein tyrosine phosphatases in immune cells. Sci Signal 3: rs1.

27. WentworthCC, AlamA, JonesRM, NusratA, NeishAS (2011) Enteric commensal bacteria induce extracellular signal-regulated kinase pathway signaling via formyl peptide receptor-dependent redox modulation of dual specific phosphatase 3. J Biol Chem 286: 38448–38455.

28. ArnoldussenYJ, LorenzoPI, PretoriusME, WaehreH, RisbergB, et al. (2008) The mitogen-activated protein kinase phosphatase vaccinia H1-related protein inhibits apoptosis in prostate cancer cells and is overexpressed in prostate cancer. Cancer Res 68: 9255–9264.

29. HenkensR, DelvenneP, ArafaM, MoutschenM, ZeddouM, et al. (2008) Cervix carcinoma is associated with an up-regulation and nuclear localization of the dual-specificity protein phosphatase VHR. BMC Cancer 8: 147.

30. JonkamCC, BansalK, TraberDL, HamahataA, MaybauerMO, et al. (2009) Pulmonary vascular permeability changes in an ovine model of methicillin-resistant Staphylococcus aureus sepsis. Crit Care 13: R19.

31. JonkamCC, LangeM, TraberDL, MaybauerDM, MaybauerMO, et al. (2009) Cardiovascular collapse and vascular permeability changes in an ovine model of methicillin-resistant Staphylococcus aureus sepsis. Shock 32: 621–625.

32. EcsediS, TothL, BalazsM (2012) Array CGH analysis of the rare laryngeal basaloid squamous cell carcinoma: a case report. Int J Clin Exp Pathol 5: 834–839.

33. van der WeydenL, WhiteJK, AdamsDJ, LoganDW (2011) The mouse genetics toolkit: revealing function and mechanism. Genome Biol 12: 224.

34. The Wellcome Trust Sanger Institute Mouse Portal [http://www.sanger.ac.uk/mouseprotal/]

35. KohdaK, IshibashiT, ShimbaraN, TanakaK, MatsudaY, et al. (1998) Characterization of the mouse PA28 activator complex gene family: complete organizations of the three member genes and a physical map of the approximately 150-kb region containing the alpha- and beta-subunit genes. J Immunol 160: 4923–4935.

36. KanaiK, AramataS, KatakamiS, YasudaK, KataokaK (2011) Proteasome activator PA28{gamma} stimulates degradation of GSK3-phosphorylated insulin transcription activator MAFA. J Mol Endocrinol 47: 119–127.

37. ChenZW, CraiuA, ShenL, KurodaMJ, IrokuUC, et al. (2000) Simian immunodeficiency virus evades a dominant epitope-specific cytotoxic T lymphocyte response through a mutation resulting in the accelerated dissociation of viral peptide and MHC class I. J Immunol 164: 6474–6479.

38. Schutze-RedelmeierMP, GournierH, Garcia-PonsF, MoussaM, JoliotAH, et al. (1996) Introduction of exogenous antigens into the MHC class I processing and presentation pathway by Drosophila antennapedia homeodomain primes cytotoxic T cells in vivo. J Immunol 157: 650–655.

39. RittirschD, FlierlMA, WardPA (2008) Harmful molecular mechanisms in sepsis. Nat Rev Immunol 8: 776–787.

40. SriskandanS, AltmannDM (2008) The immunology of sepsis. J Pathol 214: 211–223.

41. Adib-ConquyM, CavaillonJM (2009) Compensatory anti-inflammatory response syndrome. Thromb Haemost 101: 36–47.

42. van der PollT, MeijersJC (2010) Systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome in sepsis. J Innate Immun 2: 379–380.

43. XuPB, LouJS, RenY, MiaoCH, DengXM (2012) Gene expression profiling reveals the defining features of monocytes from septic patients with compensatory anti-inflammatory response syndrome. J Infect 65: 380–391.

44. RitterhoffS, FarahCM, GrabitzkiJ, LochnitG, SkuratAV, et al. (2010) The WD40-repeat protein Han11 functions as a scaffold protein to control HIPK2 and MEKK1 kinase functions. EMBO J 29: 3750–3761.

45. BouwmeesterT, BauchA, RuffnerH, AngrandPO, BergaminiG, et al. (2004) A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol 6: 97–105.

46. TaoL, WadsworthS, MercerJ, MuellerC, LynnK, et al. (2002) Opposing roles of serine/threonine kinases MEKK1 and LOK in regulating the CD28 responsive element in T-cells. Biochem J 363: 175–182.

47. Oviedo-BoysoJ, Barriga-RiveraJG, Valdez-AlarconJJ, Bravo-PatinoA, Carabez-TrejoA, et al. (2008) Internalization of Staphylococcus aureus by bovine endothelial cells is associated with the activity state of NF-kappaB and modulated by the pro-inflammatory cytokines TNF-alpha and IL-1beta. Scand J Immunol 67: 169–176.

48. LiB, LiJ, PanX, DingG, CaoH, et al. (2010) Artesunate protects sepsis model mice challenged with Staphylococcus aureus by decreasing TNF-alpha release via inhibition TLR2 and Nod2 mRNA expressions and transcription factor NF-kappaB activation. Int Immunopharmacol 10: 344–350.

49. KurthI, PammingerT, HenningsJC, SoehendraD, HuebnerAK, et al. (2009) Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nat Genet 41: 1179–1181.

50. Al-SamirS, PapadopoulosS, ScheibeRJ, MeissnerJD, CartronJP, et al. (2013) Activity and distribution of intracellular carbonic anhydrase II and their effects on the transport activity of anion exchanger AE1/SLC4A1. J Physiol 591(Pt 20): 4963–82.

51. Barneaud-RoccaD, EtchebestC, GuizouarnH (2013) Structural Model of the Anion Exchanger 1 (SLC4A1) and Identification of Transmembrane Segments Forming the Transport Site. J Biol Chem 288: 26372–26384.

52. HaitinaT, LindblomJ, RenstromT, FredrikssonR (2006) Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system. Genomics 88: 779–790.

53. YanQ, GongL, DengM, ZhangL, SunS, et al. (2010) Sumoylation activates the transcriptional activity of Pax-6, an important transcription factor for eye and brain development. Proc Natl Acad Sci U S A 107: 21034–21039.

54. YanQ, LiuWB, QinJ, LiuJ, ChenHG, et al. (2007) Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development. J Biol Chem 282: 13954–13965.

55. ZaasAK, BurkeT, ChenM, McClainM, NicholsonB, et al. (2013) A host-based RT-PCR gene expression signature to identify acute respiratory viral infection. Sci Transl Med 5: 203ra126.

56. GlickmanSW, CairnsCB, OteroRM, WoodsCW, TsalikEL, et al. (2010) Disease progression in hemodynamically stable patients presenting to the emergency department with sepsis. Acad Emerg Med 17: 383–390.

57. LangleyRJ, TsalikEL, van VelkinburghJC, GlickmanSW, RiceBJ, et al. (2013) An integrated clinico-metabolomic model improves prediction of death in sepsis. Sci Transl Med 5: 195ra195.

58. AhnSH, TsalikEL, CyrDD, ZhangY, van VelkinburghJC, et al. (2013) Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans. PLoS One 8: e48979.

59. MasonDJ, ShanmuganathanS, MortimerFC, GantVA (1998) A fluorescent Gram stain for flow cytometry and epifluorescence microscopy. Appl Environ Microbiol 64: 2681–2685.

60. ThurlowLR, HankeML, FritzT, AngleA, AldrichA, et al. (2011) Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. J Immunol 186: 6585–6596.