Rhinovirus infections are the major cause of asthma exacerbations. We hypothesised that IL-15, a cytokine implicated in innate and acquired antiviral immunity, may be deficient in asthma and important in the pathogenesis of asthma exacerbations. We investigated regulation of IL-15 induction by rhinovirus in human macrophages in vitro, IL-15 levels in bronchoalveolar lavage (BAL) fluid and IL-15 induction by rhinovirus in BAL macrophages from asthmatic and control subjects, and related these to outcomes of infection in vivo. Rhinovirus induced IL-15 in macrophages was replication-, NF-κB - and α/β interferon-dependent. BAL macrophage IL-15 induction by rhinovirus was impaired in asthmatics and inversely related to lower respiratory symptom severity during experimental rhinovirus infection. IL-15 levels in BAL fluid were also decreased in asthmatics and inversely related with airway hyperresponsiveness and with virus load during in vivo rhinovirus infection. Deficient IL-15 production in asthma may be important in the pathogenesis of asthma exacerbations.
Vyšlo v časopise: The Role of IL-15 Deficiency in the Pathogenesis of Virus-Induced Asthma Exacerbations. PLoS Pathog 7(7): e32767. doi:10.1371/journal.ppat.1002114 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002114
1. JohnstonSLPattemorePKSandersonGSmithSLampeF 1995 Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ 310 1225 1229
2. CorneJMMarshallCSmithSSchreiberJSandersonG 2002 Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet 359 831 834
3. MessageSDLaza-StancaVMalliaPParkerHLZhuJ 2008 Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production. Proc Natl Acad Sci U S A 105 13562 13567
4. WarkPAJohnstonSLBucchieriFPowellRPuddicombeS 2005 Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med 201 937 947
5. ContoliMMessageSDLaza-StancaVEdwardsMRWarkPA 2006 Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med 12 1023 1026
6. Laza-StancaVStanciuLAMessageSDEdwardsMRGernJE 2006 Rhinovirus replication in human macrophages induces NF-kappaB-dependent tumor necrosis factor alpha production. J Virol 80 8248 8258
7. CarsonWERossMEBaiocchiRAMarienMJBoianiN 1995 Endogenous production of interleukin 15 by activated human monocytes is critical for optimal production of interferon-gamma by natural killer cells in vitro. J Clin Invest 96 2578 2582
8. FawazLMSharif-AskariEMenezesJ 1999 Up-regulation of NK cytotoxic activity via IL-15 induction by different viruses: a comparative study. J Immunol 163 4473 4480
9. MussoTCalossoLZuccaMMillesimoMRavarinoD 1999 Human monocytes constitutively express membrane-bound, biologically active, and interferon-gamma-upregulated interleukin-15. Blood 93 3531 3539
10. EnnaciriJAhmadRMenezesJ 2007 Interaction of monocytic cells with respiratory syncytial virus results in activation of NF-kappaB and PKC-alpha/beta leading to up-regulation of IL-15 gene expression. J Leukoc Biol 81 625 631
11. MuroSTahaRTsicopoulosAOlivensteinRTonnelAB 2001 Expression of IL-15 in inflammatory pulmonary diseases. J Allergy Clin Immunol 108 970 975
12. Komai-KomaMMcKayAThomsonLMcSharryCChalmersGW 2001 Immuno-regulatory cytokines in asthma: IL-15 and IL-13 in induced sputum. Clin Exp Allergy 31 1441 1448
13. BoscoAEhteshamiSSternDAMartinezFD 2010 Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction. Mucosal Immunol 3 399 409
14. MatteiFSchiavoniGBelardelliFToughDF 2001 IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded RNA, or lipopolysaccharide and promotes dendritic cell activation. J Immunol 167 1179 1187
15. Gary-GouyHLebonPDalloulAH 2002 Type I interferon production by plasmacytoid dendritic cells and monocytes is triggered by viruses, but the level of production is controlled by distinct cytokines. J Interferon Cytokine Res 22 653 659
16. WashizuJNishimuraHNakamuraNNimuraYYoshikaiY 1998 The NF-kappaB binding site is essential for transcriptional activation of the IL-15 gene. Immunogenetics 48 1 7
17. TaniguchiTOgasawaraKTakaokaATanakaN 2001 IRF family of transcription factors as regulators of host defense. Annu Rev Immunol 19 623 655
18. AhmadREnnaciriJCordeiroPEl BassamSMenezesJ 2007 Herpes simplex virus-1 up-regulates IL-15 gene expression in monocytic cells through the activation of protein tyrosine kinase and PKC zeta/lambda signaling pathways. J Mol Biol 367 25 35
19. SirenJPirhonenJJulkunenIMatikainenS 2005 IFN-alpha regulates TLR-dependent gene expression of IFN-alpha, IFN-beta, IL-28, and IL-29. J Immunol 174 1932 1937
20. TamuraTYanaiHSavitskyDTaniguchiT 2008 The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 26 535 584
21. PapadopoulosNGStanciuLAPapiAHolgateSTJohnstonSL 2002 Rhinovirus-induced alterations on peripheral blood mononuclear cell phenotype and costimulatory molecule expression in normal and atopic asthmatic subjects. Clin Exp Allergy 32 537 542
22. PapadopoulosNGStanciuLAPapiAHolgateSTJohnstonSL 2002 A defective type 1 response to rhinovirus in atopic asthma. Thorax 57 328 332
23. BeckerTCWherryEJBooneDMurali-KrishnaKAntiaR 2002 Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J Exp Med 195 1541 1548
24. JinushiMTakeharaTTatsumiTKantoTGrohV 2003 Autocrine/paracrine IL-15 that is required for type I IFN-mediated dendritic cell expression of MHC class I-related chain A and B is impaired in hepatitis C virus infection. J Immunol 171 5423 5429
25. FoongYYJansDARolphMSGahanMEMahalingamS 2009 Interleukin-15 mediates potent antiviral responses via an interferon-dependent mechanism. Virology 393 228 237
26. KutzlerMARobinsonTMChattergoonMAChooDKChooAY 2005 Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol 175 112 123
27. EdwardsMRBartlettNWClarkeDBirrellMBelvisiM 2009 Targeting the NF-kappaB pathway in asthma and chronic obstructive pulmonary disease. Pharmacol Ther 121 1 13
28. JainSKamimotoLBramleyAMSchmitzAMBenoitSR 2009 Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 361 1935 1944
29. JohnstonSLPapiABatesPJMastronardeJGMonickMM 1998 Low grade rhinovirus infection induces a prolonged release of IL-8 in pulmonary epithelium. J Immunol 160 6172 6181
30. HewsonCAEdbrookeMRJohnstonSL 2004 PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms. J Mol Biol 344 683 695
31. AghanouriRGhaneiMAslaniJKeivani-AmineHRastegarF 2004 Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard. Am J Physiol Lung Cell Mol Physiol 287 L1160 1164
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
