Bacterial Pathogens Activate a Common Inflammatory Pathway through IFNλ Regulation of PDCD4

English version České info

The type III interferon (IFNλ) receptor IL-28R is abundantly expressed in the respiratory tract and has been shown essential for host defense against some viral pathogens, however no data are available concerning its role in the innate immune response to bacterial pathogens. Staphylococcus aureus and Pseudomonas aeruginosa induced significant production of IFNλ in the lung, and clearance of these bacteria from the lung was significantly increased in IL-28R null mice compared to controls. Improved bacterial clearance correlated with reduced lung pathology and a reduced ratio of pro- vs anti-inflammatory cytokines in the airway. In human epithelial cells IFNλ inhibited miR-21 via STAT3 resulting in upregulation of PDCD4, a protein known to promote inflammatory signaling. In vivo 18 hours following infection with either pathogen, miR-21 was significantly reduced and PDCD4 increased in the lungs of wild type compared to IL-28R null mice. Infection of PDCD4 null mice with USA300 resulted in improved clearance, reduced pathology, and reduced inflammatory cytokine production. These data suggest that during bacterial pneumonia IFNλ promotes inflammation by inhibiting miR-21 regulation of PDCD4.

Vyšlo v časopise: Bacterial Pathogens Activate a Common Inflammatory Pathway through IFNλ Regulation of PDCD4. PLoS Pathog 9(10): e32767. doi:10.1371/journal.ppat.1003682
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003682

Souhrn

Zdroje

1. ParkerD, CohenTS, AlhedeM, HarfenistBS, MartinFJ, et al. (2012) Induction of type I interferon signaling by Pseudomonas aeruginosa is diminished in cystic fibrosis epithelial cells. Am J Respir Cell Mol Biol 46: 6–13 doi:10.1165/rcmb.2011-0080OC

2. ParkerD, PrinceA (2012) Staphylococcus aureus induces type I IFN signaling in dendritic cells via TLR9. J Immunol 189: 4040–4046 doi:10.4049/jimmunol.1201055

3. ParkerD, MartinFJ, SoongG, HarfenistBS, AguilarJL, et al. (2011) Streptococcus pneumoniae DNA initiates type I interferon signaling in the respiratory tract. mBio 2: e00016–11 doi:10.1128/mBio.00016-11

4. DavidM (2010) Interferons and microRNAs. Journal of Interferon & Cytokine Research 30: 825–828 doi:10.1089/jir.2010.0080

5. TrinchieriG (2010) Type I interferon: friend or foe? Journal of Experimental Medicine 207: 2053–2063 doi:10.1084/jem.20101664

6. HeL, HannonGJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5: 522–531 doi:10.1038/nrg1379

7. MaX, Becker BuscagliaLE, BarkerJR, LiY (2011) MicroRNAs in NF-kappaB signaling. J Mol Cell Biol 3: 159–166 doi:10.1093/jmcb/mjr007

8. O'NeillLA, SheedyFJ, McCoyCE (2011) MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol 11: 163–175 doi:10.1038/nri2957

9. QuinnSR, O'NeillLA (2011) A trio of microRNAs that control Toll-like receptor signalling. International Immunology 23: 421–425 doi:10.1093/intimm/dxr034

10. YasudaM, SchmidT, RübsamenD, ColburnNH, IrieK, et al. (2010) Downregulation of programmed cell death 4 by inflammatory conditions contributes to the generation of the tumor promoting microenvironment. Mol Carcinog 49: 837–848 doi:10.1002/mc.20660

11. CohenTS, PrinceAS (2013) Activation of inflammasome signaling mediates pathology of acute P. aeruginosa pneumonia. J Clin Invest 123: 1630–1637 doi:10.1172/JCI66142DS1

12. FrankelLB, ChristoffersenNR, JacobsenA, LindowM, KroghA, et al. (2008) Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 283: 1026–1033 doi:10.1074/jbc.M707224200

13. MartinFJ, GómezMI, WetzelDM, MemmiG, O'SeaghdhaM, et al. (2009) Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A. J Clin Invest. 119: 1931–1939.

14. MartinFJ, ParkerD, HarfenistBS, SoongG, PrinceA (2011) Participation of CD11c(+) leukocytes in methicillin-resistant Staphylococcus aureus clearance from the lung. Infect Immun 79: 1898–1904 doi:10.1128/IAI.01299-10

15. CarriganSO, JunkinsR, YangYJ, MacneilA, RichardsonC, et al. (2010) IFN regulatory factor 3 contributes to the host response during Pseudomonas aeruginosa lung infection in mice. J Immunol 185: 3602–3609 doi:10.4049/jimmunol.0903429

16. PowerMR, LiB, YamamotoM, AkiraS, LinT-J (2007) A role of Toll-IL-1 receptor domain-containing adaptor-inducing IFN-beta in the host response to Pseudomonas aeruginosa lung infection in mice. J Immunol 178: 3170–3176.

17. DennisMD, JeffersonLS, KimballSR (2012) Role of p70S6K1-mediated Phosphorylation of eIF4B and PDCD4 Proteins in the Regulation of Protein Synthesis. Journal of Biological Chemistry 287: 42890–42899 doi:10.1074/jbc.M112.404822

18. KotenkoSV, GallagherG, BaurinVV, Lewis-AntesA, ShenM, et al. (2003) IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4: 69–77 doi:10.1038/ni875

19. LiwakU, ThakorN, JordanLE, RoyR, LewisSM, et al. (2012) Tumor Suppressor PDCD4 Represses Internal Ribosome Entry Site-Mediated Translation of Antiapoptotic Proteins and Is Regulated by S6 Kinase 2. Mol Cell Biol 32: 1818–1829 doi:10.1128/MCB.06317-11

20. SheppardP, KindsvogelW, XuW, HendersonK, SchlutsmeyerS, et al. (2003) IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 4: 63–68 doi:10.1038/ni873

21. de WeerdNA, NguyenT (2012) The interferons and their receptors--distribution and regulation. Immunology and Cell Biology 90: 483–491 doi:10.1038/icb.2012.9

22. KroczynskaB, SharmaB, EklundEA, FishEN, PlataniasLC (2012) Regulatory effects of programmed cell death 4 (PDCD4) protein in interferon (IFN)-stimulated gene expression and generation of type I IFN responses. Mol Cell Biol 32: 2809–2822 doi:10.1128/MCB.00310-12

23. MeagerA, VisvalingamK, DilgerP, BryanD, WadhwaM (2005) Biological activity of interleukins-28 and -29: comparison with type I interferons. Cytokine 31: 109–118 doi:10.1016/j.cyto.2005.04.003

24. MaherSG, SheikhF, ScarzelloAJ, Romero-WeaverAL, BakerDP, et al. (2008) IFNalpha and IFNlambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity. Cancer Biol Ther 7: 1109–1115.

25. AnkN, IversenMB, BartholdyC, StaeheliP, HartmannR, et al. (2008) An important role for type III interferon (IFN-λ/IL-28) in TLR-induced antiviral activity. J Immunol 180: 2474–2485.

26. ZhouZ, HammingOJ, AnkN, PaludanSR, NielsenAL, et al. (2007) Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signaling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases. J Virol 81: 7749–7758 doi:10.1128/JVI.02438-06

27. PulvererJE, RandU, LienenklausS, KugelD, ZietaraN, et al. (2010) Temporal and spatial resolution of type I and III interferon responses in vivo. J Virol 84: 8626–8638 doi:10.1128/JVI.00303-10

28. SommereynsC, PaulS, StaeheliP, MichielsT (2008) IFN-lambda (IFN-λ) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathog 4: e1000017 doi:10.1371/journal.ppat.1000017

29. MerlineR, MorethK, BeckmannJ, NastaseMV, Zeng-BrouwersJ, et al. (2011) Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and microRNA-21. Science Signaling 4: ra75–ra75 Available: http://stke.sciencemag.org/cgi/content/abstract/sigtrans4/199/ra75.

30. WangJ, Oberley-DeeganR, WangS, NikradM, FunkCJ, et al. (2009) Differentiated human alveolar type II cells secrete antiviral IL-29 (IFN-lambda 1) in response to influenza A infection. J Immunol 182: 1296–1304.

31. SheedyFJ, Palsson-McDermottE, HennessyEJ, MartinC, O'LearyJJ, et al. (2009) Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 11: 141–147 doi:10.1038/ni.1828

32. JewellNA, ClineT, MertzSE, SmirnovSV, FlanoE, et al. (2010) Lambda interferon is the predominant interferon induced by influenza A virus infection in vivo. J Virol 84: 11515–11522 doi:10.1128/JVI.01703-09

33. YangHS, JansenAP, NairR, ShibaharaK, VermaAK, et al. (2001) A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation. Oncogene 20: 669–676 doi:10.1038/sj.onc.1204137

34. KoltsidaO, HausdingM, StavropoulosA, KochS, TzelepisG, et al. (2011) IL-28A (IFN-λ2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease. EMBO Mol Med 3: 348–361 doi:10.1002/emmm.201100142

35. GallagherG, MegjugoracNJ, YuRY, EskdaleJ, GallagherGE, et al. (2010) The lambda interferons: guardians of the immune-epithelial interface and the T-helper 2 response. Journal of Interferon & Cytokine Research 30: 603–615 doi:10.1089/jir.2010.0081

36. PekarekV, SrinivasS, EskdaleJ, GallagherG (2007) Interferon lambda-1 (IFN-λ1/IL-29) induces ELR(-) CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-gamma-independent manner. Genes Immun 8: 177–180 doi:10.1038/sj.gene.6364372

37. ChastreJ, FagonJ-Y (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165: 867–903.

38. Centers for Disease Control and Prevention (CDC) (2003) Methicillin-resistant Staphylococcus aureus infections in correctional facilities---Georgia, California, and Texas, 2001-2003. MMWR Morb Mortal Wkly Rep 52: 992–996.

39. MarcelloT, GrakouiA, Barba-SpaethG, MachlinES, KotenkoSV, et al. (2006) Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 131: 1887–1898 doi:10.1053/j.gastro.2006.09.052

40. DoyleSE, SchreckhiseH, Khuu-DuongK, HendersonK, RoslerR, et al. (2006) Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytes. Hepatology 44: 896–906 doi:10.1002/hep.21312

41. GómezMI, SeaghdhaMO, PrinceAS (2007) Staphylococcus aureus protein A activates TACE through EGFR-dependent signaling. EMBO J 26: 701–709 doi:10.1038/sj.emboj.7601554

42. GómezMI, LeeA, ReddyB, MuirA, SoongG, et al. (2004) Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med 10: 842–848 doi:10.1038/nm1079

43. GómezMI, O'SeaghdhaM, MagargeeM, FosterTJ, PrinceAS (2006) Staphylococcus aureus protein A activates TNFR1 signaling through conserved IgG binding domains. J Biol Chem 281: 20190–20196.

44. PalamarchukA, EfanovA, MaximovV, AqeilanRI, CroceCM, et al. (2005) Akt phosphorylates and regulates Pdcd4 tumor suppressor protein. Cancer Res 65: 11282–11286 doi:10.1158/0008-5472.CAN-05-3469

45. WedekenL, SinghP, KlempnauerK-H (2011) Tumor suppressor protein Pdcd4 inhibits translation of p53 mRNA. Journal of Biological Chemistry 286: 42855–42862 doi:10.1074/jbc.M111.269456

46. WedekenL, OhnheiserJ, HirschiB, WethkampN, KlempnauerK-H (2010) Association of tumor suppressor protein Pdcd4 with ribosomes is mediated by protein-protein and protein-RNA interactions. Genes & Cancer 1: 293–301 doi:10.1177/1947601910364227

47. SatoA, OhtsukiM, HataM, KobayashiE, MurakamiT (2006) Antitumor activity of IFN-lambda in murine tumor models. J Immunol 176: 7686–7694.

48. LasfarA, Lewis-AntesA, SmirnovSV, AnanthaS, AbushahbaW, et al. (2006) Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma. Cancer Res 66: 4468–4477 doi:10.1158/0008-5472.CAN-05-3653

49. DickensheetsH, SheikhF, ParkO, GaoB, DonnellyRP (2013) Interferon-lambda (IFN-λ) induces signal transduction and gene expression in human hepatocytes, but not in lymphocytes or monocytes. J Leukoc Biol 93: 377–385 doi:10.1189/jlb.0812395

50. GeD, FellayJ, ThompsonAJ, SimonJS, ShiannaKV, et al. (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461: 399–401 doi:10.1038/nature08309

51. LebretonA, LakisicG, JobV, FritschL, ThamTN, et al. (2011) A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response. Science 331: 1319–1321 doi:10.1126/science.1200120

52. SuzukiC, GarcesRG, EdmondsKA, HillerS, HybertsSG, et al. (2008) PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains. PNAS 105: 3274–3279 doi:10.1073/pnas.0712235105

53. LiuX, ZhanZ, XuL, MaF, LiD, et al. (2010) MicroRNA-148/152 impair innate response and antigen presentation of TLR-triggered dendritic cells by targeting CaMKIIα. J Immunol 185: 7244–7251 doi:10.4049/jimmunol.1001573

54. LiuPT, WheelwrightM, TelesR, KomisopoulouE, EdfeldtK, et al. (2012) MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy. Nat Med 18: 267–273 doi:10.1038/nm.2584

55. CaseSR, MartinRJ, JiangD, MinorMN, ChuHW (2011) MicroRNA-21 inhibits toll-like receptor 2 agonist-induced lung inflammation in mice. Exp Lung Res 37: 500–508 doi:10.3109/01902148.2011.596895

56. LuTX, HartnerJ, LimE-J, FabryV, MinglerMK, et al. (2011) MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J Immunol 187: 3362–3373 doi:10.4049/jimmunol.1101235

57. RuanQ, WangT, KameswaranV, WeiQ, JohnsonDS, et al. (2011) The microRNA-21-PDCD4 axis prevents type 1 diabetes by blocking pancreatic {beta} cell death. PNAS 108: 12030–12035 doi:10.1073/pnas.1101450108/-/DCSupplemental/pnas.201101450SI.pdf

58. ParkerD, PrinceA (2013) Epithelial uptake of flagella initiates proinflammatory signaling. PLoS ONE 8: e59932 doi:10.1371/journal.pone.0059932.g005

59. MijaresLA, WangdiT, SokolC, HomerR, MedzhitovR, et al. (2011) Airway epithelial MyD88 restores control of Pseudomonas aeruginosa murine infection via an IL-1-dependent pathway. J Immunol 186: 7080–7088 doi:10.4049/jimmunol.1003687

60. ChunJ, PrinceA (2009) TLR2-induced calpain cleavage of epithelial junctional proteins facilitates leukocyte transmigration. Cell Host Microbe 5: 47–58 doi:10.1016/j.chom.2008.11.009