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Bacterial RNA as a signal to eukaryotic cells as part of the infection process

DISCOVERIES (ISSN 2359-7232), 2016, October-December issue


Simonov D, Swift S, Blenkiron C, Phillips AR. Bacterial RNA as a signal to eukaryotic cells as part of the infection process. Discoveries 2016, Oct-Dec; 4(4): e70. DOI: 10.15190/d.2016.17

Submitted: December 27th, 2016; Revised: December 31st, 2016; Accepted: December 31st, 2016; Published: December 31st, 2016;

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Bacterial RNA as a signal to eukaryotic cells  as part of the infection process

Denis Simonov (1,2) Simon Swift (1,*), Cherie Blenkiron (1,2), Anthony R. Phillips (2,3,4) 

(1) Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand;

(2) Department of Surgery, University of Auckland, Auckland, New Zealand;

(3) School of Biological Sciences, University of Auckland, Auckland, New Zealand;

(4) Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand;

*Correspondence to: Simon Swift, PhD, Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Phone: +64 9 373 7599 ext 86273; E-mail: s.swift@auckland.ac.nz


The discovery of regulatory RNA has identified an underappreciated area for microbial subversion of the host. There is increasing evidence that RNA can be delivered from bacteria to host cells associated with membrane vesicles or by direct release from intracellular bacteria. Once inside the host cell, RNA can act by activating sequence-independent receptors of the innate immune system, where recent findings suggest this can be more than simple pathogen detection, and may contribute to the subversion of immune responses. Sequence specific effects are also being proposed, with examples from nematode, plant and human models providing support for the proposition that bacteria-to-human RNA signaling and the subversion of host gene expression may occur.

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1. Sharp GWG, Hynie S. Stimulation of Intestinal Adenyl Cyclase by Cholera Toxin. Nature 1971;229:266–9. doi:10.1038/229266a0.

2. Agbor TA, McCormick BA. Salmonella effectors: important players modulating host cell function during infection. Cell Microbiol 2011;13:1858–69. doi:10.1111/j.1462-5822.2011.01701.x.

3. Fuqua WC, Winans SC, Greenberg EP. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 1994;176:269–75. doi:10.1128/jb.176. 2.269-275.1994.

4. Rajput A, Kaur K, Kumar M. SigMol: repertoire of quorum sensing signaling molecules in prokaryotes. Nucleic Acids Res  2016;44:D634–9. doi:10.1093/ nar/gkv1076.

5. Telford G, Wheeler D, Williams P, Tomkins PT, Appleby P, Sewell H, et al. The Pseudomonas aeruginosa Quorum-Sensing Signal Molecule N-(3-Oxododecanoyl)-l-Homoserine Lactone Has Immunomodulatory Activity. Infect Immun 1998; 66:36–42.

6. Williams P. Quorum sensing, communication and cross-kingdom signalling in the bacterial world. Microbiology 2007;153:3923–38. doi:10.1099/mic.0. 2007/012856-0.

7. Hughes DT, Sperandio V. Inter-kingdom signalling: communication between bacteria and their hosts. Nat Rev Microbiol 2008;6:111–20. doi:10.1038/ nrmicro1836.

8. Pfeffer S. Identification of Virus-Encoded MicroRNAs. Science 2004;304:734–6. doi:10.1126/ science.1096781.

9. Cullen BR. Viruses and microRNAs: RISCy interactions with serious consequences. Genes Dev 2011;25:1881–94. doi:10.1101/gad.17352611.

10. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654–9.

11. Eigenbrod T, Dalpke AH. Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses. J Immunol 2015;195:411–8. doi:10.4049/ jimmunol.1500530.

12. Koeppen K, Hampton TH, Jarek M, Scharfe M, Gerber SA, Mielcarz DW, et al. A Novel Mechanism of Host-Pathogen Interaction through sRNA in Bacterial Outer Membrane Vesicles. PLOS Pathog 2016;12:e1005672. doi:10.1371/journal.ppat.1005 672.

13. Blenkiron C, Simonov D, Muthukaruppan A, Tsai P, Dauros P, Green S, et al. Uropathogenic Escherichia coli Releases Extracellular Vesicles That Are Associated with RNA. PLoS One 2016;11:e0160440. doi:10.1371/journal.pone.0160440.

14. Deshmukh SD, Kremer B, Freudenberg M, Bauer S, Golenbock DT, Henneke P. Macrophages recognize streptococci through bacterial single-stranded RNA. EMBO Rep 2011;12:71–6. doi:10.1038/embor.2010. 189.

15. Mancuso G, Gambuzza M, Midiri A, Biondo C, Papasergi S, Akira S, et al. Bacterial recognition by TLR7 in the lysosomes   of conventional dendritic cells. Nat Immunol 2009;10:587–94. doi:10.1038/ ni.1733.

16. Spencer JD, Schwaderer AL, Wang H, Bartz J, Kline J, Eichler T, et al. Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract. Kidney Int 2013;83:615–25. doi:10.1038/ki.2012.410.

17. Becknell B, Eichler TE, Beceiro S, Li B, Easterling RS, Carpenter AR, et al. Ribonucleases 6 and 7 have antimicrobial function in the human and murine  urinary tract. Kidney Int 2015;87:151–61. doi:10.1038/ki.2014.268.

18. Harder J. RNase 7, a Novel Innate Immune Defense Antimicrobial Protein of Healthy Human Skin. J Biol Chem 2002;277:46779–84. doi:10.1074/jbc. M207587200.

19. Reithmayer K, Meyer KC, Kleditzsch P, Tiede S, Uppalapati SK, Gläser R, et al. Human hair follicle epithelium has an antimicrobial defence system that includes the inducible antimicrobial peptide psoriasin (S100A7) and RNase 7. Br J Dermatol 2009;161:78–89. doi:10.1111/j.1365-2133.2009.09154.x.

20. Kamm RC, Smith AG. Ribonuclease activity in human plasma. Clin Biochem 1972;5:198–200. doi:10.1016/S0009-9120(72)80033-X.

21. Blank A, Dekker CA. Ribonucleases of human serum, urine, cerebrospinal fluid, and leukocytes. Activity staining following electrophoresis in sodium dodecyl sulfate-polyacrylamide gels. Biochemistry 1981;20:2261–7. doi:10.1021/bi00511a030.

22. Brencicova E, Diebold SS. Nucleic acids and endosomal pattern recognition: how to tell friend from foe? Front Cell Infect Microbiol 2013;3:37. doi:10.3389/fcimb.2013.00037.

23. Creemers EE, Tijsen AJ, Pinto YM. Circulating MicroRNAs: Novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res 2012;110:483–95. doi:10.1161/CIRCRESAHA.111. 247452.

24. Kieft JS, Rabe JL, Chapman EG. New hypotheses derived from the structure of a flaviviral Xrn1-resistant RNA: Conservation, folding, and host adaptation. RNA Biol 2015;12:1169–77. doi:10. 1080/15476286.2015.1094599.

25. Wang K, Li H, Yuan Y, Etheridge A, Zhou Y, Huang D, et al. The Complex Exogenous RNA Spectra in Human Plasma: An Interface with Human Gut Biota? PLoS One 2012;7. doi:10.1371/journal.pone. 0051009.

26. Semenov D V., Baryakin DN, Brenner E V., Kurilshikov AM, Vasiliev G V., Bryzgalov L a., et al. Unbiased approach to profile the variety of small non-coding RNA of human blood plasma with massively parallel sequencing technology. Expert Opin Biol Ther 2012;12:S43–51. doi:10.1517/ 14712598.2012.679653.

27. Beatty M, Guduric-Fuchs J, Brown E, Bridgett S, Chakravarthy U, Hogg RE, et al. Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma. BMC Genomics 2014;15:933. doi:10.1186/1471-2164-15-933.

28. Leung RK-K, Wu Y-K. Circulating microbial RNA and health. Sci Rep 2015;5:16814. doi:10.1038/ srep16814.

29. Freedman JE, Gerstein M, Mick E, Rozowsky J, Levy D, Kitchen R, et al. Diverse human extracellular RNAs are widely detected in human plasma. Nat Commun 2016;7:11106. doi:10.1038 /ncomms11106.

30. Lee P, Tan KS. Fusobacterium nucleatum activates the immune response through retinoic acid-inducible gene I. J Dent Res 2014;93:162–8. doi:10.1177/ 0022034513516346.

31. Ghosal A, Upadhyaya BB, Heintz-buschart A, Desai S, Yusuf D, Huang D, et al. The extracellular RNA complement of Escherichia coli 2015. doi:10.1002/mbo3.235.

32. Obregón-Henao A, Duque-Correa M a., Rojas M, García LF, Brennan PJ, Ortiz BL, et al. Stable extracellular RNA fragments of mycobacterium tuberculosis induce early apoptosis in human monocytes via a Caspase-8 dependent mechanism. PLoS One 2012;7. doi:10.1371/journal.pone. 0029970.

33. Ho M-H, Chen C-H, Goodwin JS, Wang B-Y, Xie H. Functional Advantages of Porphyromonas gingivalis Vesicles. PLoS One 2015;10:e0123448. doi:10.1371/journal.pone.0123448.

34. Sjöström AE, Sandblad L, Uhlin BE, Wai SN. Membrane vesicle-mediated release of bacterial RNA. Nat Publ Gr 2015:1–10. doi:10.1038/ srep15329.

35. Turnbull L, Toyofuku M, Hynen AL, Kurosawa M, Pessi G, Petty NK, et al. Explosive cell lysis as a mechanism for the biogenesis of bacterial membrane vesicles and biofilms. Nat Commun 2016;7:11220. doi:10.1038/ncomms11220.

36. Brown L, Wolf JM, Prados-rosales R, Casadevall A. Through the wall : extracellular vesicles in Gram-positive bacteria , mycobacteria and fungi. Nat Publ Gr 2015;13:620–30. doi:10.1038/nrmicro3480.

37. Schwechheimer C, Kuehn MJ. Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat Rev Microbiol 2015;13:605–19. doi:10.1038/nrmicro3525.

38. Kim JH, Lee J, Park J, Gho YS. Gram-negative and Gram-positive bacterial extracellular vesicles. Semin Cell Dev Biol 2015;40:97–104. doi:10.1016/ j.semcdb.2015.02.006.

39. Pathirana R, Kaparakis-Liaskos M. Bacterial membrane vesicles: biogenesis, immune regulation and pathogenesis. Cell Microbiol 2016:1–12. doi:10.1111/cmi.12658.

40. Laughlin RC, Alaniz RC. Outer membrane vesicles in service as protein shuttles, biotic defenders, and immunological doppelgangers. Gut Microbes 2016;7:1–5. doi:10.1080/19490976.2016.1222345.

41. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654–9. doi:10.1038/ncb1596.

42. Zomer A, Vendrig T, Hopmans ES, van Eijndhoven M, Middeldorp JM, Pegtel DM. Exosomes: Fit to deliver small RNA. Commun Integr Biol 2010;3:447–50. doi:10.4161/cib.3.5.12339.

43. Pegtel DM, Cosmopoulos K, Thorley-Lawson D a, van Eijndhoven M a J, Hopmans ES, Lindenberg JL, et al. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci 2010;107:6328–33. doi:10.1073/pnas.0914843107.

44. Kulp A, Kuehn MJ. Biological Functions and Biogenesis of Secreted Bacterial Outer Membrane Vesicles. Annu Rev Microbiol 2010;64:163–84. doi:10.1146/annurev.micro.091208.073413.

45. Schertzer JW, Whiteley M. A Bilayer-Couple Model of Bacterial Outer Membrane Vesicle Biogenesis. mBio  2012;3. doi:10.1128/mBio.00297-11.

46. Roier S, Zingl FG, Cakar F, Durakovic S, Kohl P, Eichmann TO, et al. A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria. Nat Commun 2016;7:10515. doi:10.1038/ncomms10515.

47. Bayles KW. Bacterial programmed cell death: making sense of a paradox. Nat Rev Microbiol 2013;12:63–9. doi:10.1038/nrmicro3136.

48. Bomberger JM, MacEachran DP, Coutermarsh B a., Ye S, O’Toole G a., Stanton B a. Long-distance delivery of bacterial virulence factors by pseudomonas aeruginosa outer membrane vesicles. PLoS Pathog 2009;5. doi:10.1371/journal. ppat.1000382.

49. Bielaszewska M, Rüter C, Kunsmann L, Greune L, Bauwens A, Zhang W, et al. Enterohemorrhagic Escherichia coli Hemolysin Employs Outer Membrane Vesicles to Target Mitochondria and Cause Endothelial and Epithelial Apoptosis. PLoS Pathog 2013;9:1–30. doi:10.1371/journal.ppat.1003797.

50. Kaparakis M, Turnbull L, Carneiro L, Firth S, Coleman HA, Parkington HC, et al. Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Cell Microbiol 2010;12:372–85. doi:10.1111/j.1462-5822.2009.01404.x.

51. Mondal A, Tapader R, Chatterjee NS, Ghosh A, Sinha R, Koley H, et al. Cytotoxic and Inflammatory responses induced by Outer Membrane Vesicles-associated biologically active Proteases from Vibrio cholerae. Infect Immun 2016;84:IAI.01365-15. doi:10.1128/IAI.01365-15.

52. Olofsson A, Skalman LN, Obi I, Lundmark R, Arnqvist A. Uptake of helicobacter pylori vesicles is facilitated by clathrin- dependent and clathrin-independent endocytic pathways. MBio 2014;5:1–12. doi:10.1128/mBio.00979-14.

53. Parker H, Chitcholtan K, Hampton MB, Keenan JI. Uptake of Helicobacter pylori outer membrane vesicles by gastric epithelial cells. Infect Immun 2010;78:5054–61. doi:10.1128/IAI.00299-10.

54. Pollak CN, Delpino MV, Fossati CA, Baldi PC. Outer Membrane Vesicles from Brucella abortus Promote Bacterial Internalization by Human Monocytes and Modulate Their Innate Immune Response 2012;7. doi:10.1371/journal.pone.0050214.

55. Thay B, Damm A, Kufer TA, Wai SN, Oscarsson J. Aggregatibacter actinomycetemcomitans outer membrane vesicles are internalized in human host cells and trigger NOD1- and NOD2-dependent NF-κB activation. Infect Immun 2014;82:4034–46. doi:10.1128/IAI.01980-14.

56. Kunsmann L, Rüter C, Bauwens A, Greune L, Glüder M, Kemper B, et al. Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain. Sci Rep 2015;5:13252. doi:10.1038/srep13252.

57. Sha W, Mitoma H, Hanabuchi S, Bao M, Weng L, Sugimoto N, et al. Human NLRP3 inflammasome senses multiple types of bacterial RNAs. Proc Natl Acad Sci 2014;111:16059–64. doi:10.1073/pnas.1412487111.

58. Eigenbrod T, Franchi L, Muñoz-Planillo R, Kirschning CJ, Freudenberg M a, Núñez G, et al. Bacterial RNA mediates activation of caspase-1 and IL-1β release independently of TLRs 3, 7, 9 and TRIF but is dependent on UNC93B. J Immunol 2012;189:328–36. doi:10.4049/jimmunol.1103258.

59. Hagmann CA, Herzner AM, Abdullah Z, Zillinger T, Jakobs C, Schuberth C, et al. RIG-I Detects Triphosphorylated RNA of Listeria monocytogenes during Infection in Non-Immune Cells 2013;8:1–11. doi:10.1371/journal.pone.0062872.

60. Hagmann CA, Herzner  a. M, Abdullah Z, Zillinger T, Jakobs C, Schuberth C, et al. RIG-I Detects Triphosphorylated RNA of Listeria monocytogenes during Infection in Non-Immune Cells. PLoS One 2013;8:1–11. doi:10.1371/journal.pone.0062872.

61. Cervantes JL, Vake CJ La, Weinerman B, Luu S, O ’connell C, Verardi PH, et al. Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes. J Leukoc Biol 2013;94:1231–41. doi:10.1189/jlb. 0413206.

62. Sander LE, Davis MJ, Boekschoten M V, Amsen D, Dascher CC, Ryffel B, et al. Detection of prokaryotic mRNA signifies microbial viability and promotes immunity. Nature 2011;474:385–9. doi:10.1038/ nature10072.

63. Gupta R, Ghosh S, Monks B, DeOliveira RB, Tzeng TC, Kalantari P, et al. RNA and β-hemolysin of group B Streptococcus induce interleukin-1β (IL-1β) by activating NLRP3 inflammasomes in mouse macrophages. J Biol Chem 2014;289:13701–5. doi:10.1074/jbc.C114.548982.

64. Gupta R, Ghosh S, Monks B, Deoliveira R, Tzeng T, Kalantari P, et al. RNA and β-hemolysin of Group B streptococcus induce IL-1β by activating NLRP3 inflammasomes in mouse macrophages. J Biol Chem 2014:0–11. doi:10.1074/jbc.C114.548982.

65. Kailasan Vanaja S, Rathinam VAK, Atianand MK, Kalantari P, Skehan B, Fitzgerald KA, et al. Bacterial RNA:DNA hybrids are activators of the NLRP3 inflammasome. Proc Natl Acad Sci U S A 2014;111:7765–70. doi:10.1073/pnas.1400075111.

66. Cervantes JL, La Vake CJ, Weinerman B, Luu S, O’Connell C, Verardi PH, et al. Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes. J Leukoc Biol 2013;94:1231–41. doi:10.1189/jlb .0413206.

67. Eigenbrod T, Pelka K, Latz E, Kreikemeyer B, Dalpke AH. TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes. J Immunol 2015;195:1092–9. doi:10.4049/jimmunol.1403173.

68. Leonard JN, Ghirlando R, Askins J, Bell JK, Margulies DH, Davies DR, et al. The TLR3 signaling complex forms by cooperative receptor dimerization. Proc Natl Acad Sci 2008;105:258–63. doi:10.1073/ pnas.0710779105.

69. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004;303:1529–31. doi:10.1126/science. 1093616.

70. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004;303:1526–9. doi:10.1126/science.1093620.

71. Geyer M, Pelka K, Latz E. Synergistic activation of Toll-like receptor 8 by two RNA degradation products. Nat Struct Mol Biol 2015;22:99–101. doi:10.1038/nsmb.2967.

72. Nishibayashi R, Inoue R, Harada Y, Watanabe T, Makioka Y, Ushida K. RNA of Enterococcus faecalis Strain EC-12 Is a Major Component Inducing Interleukin-12 Production from Human Monocytic Cells. PLoS One 2015;10:e0129806. doi:10.1371/ journal.pone.0129806.

73. Yoneyama M, Onomoto K, Jogi M, Akaboshi T, Fujita T. Viral RNA detection by RIG-I-like receptors. Curr Opin Immunol 2015;32:48–53. doi:10.1016/j.coi.2014.12.012.

74. Kanneganti T-D, Ozören N, Body-Malapel M, Amer A, Park J-H, Franchi L, et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 2006;440:233–6. doi:10. 1038/nature04517.

75. Kailasan Vanaja S, Rathinam VAK, Atianand MK, Kalantari P, Skehan B, Fitzgerald KA, et al. Bacterial RNA:DNA hybrids are activators of the NLRP3 inflammasome. Proc Natl Acad Sci U S A 2014;111:7765–70. doi:10.1073/pnas.1400075111.

76. Jo E-K, Kim JK, Shin D-M, Sasakawa C. Molecular mechanisms regulating NLRP3 inflammasome activation. Cell Mol Immunol 2016;13:148–59. doi:10.1038/cmi.2015.95.

77. Love AC, Schwartz I, Petzke MM. Borrelia burgdorferi RNA induces type I and III interferons via toll-like receptor 7 and contributes to production of NF-kB-dependent cytokines. Infect Immun 2014;82:2405–16. doi:10.1128/IAI.01617-14.

78. Gratz N, Hartweger H, Matt U, Kratochvill F, Janos M, Sigel S, et al. Type I Interferon Production Induced By Streptococcus Pyogenes-Derived Nucleic Acids is Required for Host Protection. PLoS Pathog 2011;7:1–16. doi:10.1371/journal.ppat.1001345.

79. Gehrig S, Eberle M-E, Botschen F, Rimbach K, Eberle F, Eigenbrod T, et al. Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity. J Exp Med 2012;209:225–33. doi:10.1084/jem.20111044.

80. Eberle F, Sirin M, Binder M, Dalpke AH. Bacterial RNA is recognized by different sets of immunoreceptors. Eur J Immunol 2009;39:2537–47. doi:10.1002/eji.200838978.

81. Karikó K, Buckstein M, Ni H, Weissman D. Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 2005;23:165–75. doi:10.1016/j.immuni.2005.06.008.

82. Koski GK, Kariko K, Xu S, Weissman D, Cohen P a, Czerniecki BJ. Cutting Edge: Innate Immune System Discriminates between RNA Containing Bacterial versus Eukaryotic Structural Features That Prime for High-Level IL-12 Secretion by Dendritic Cells. J Immunol 2004;172:3989–93. doi:10.4049/jimmunol. 172.7.3989.

83. Eigenbrod T, Dalpke AH. Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses. J Immunol 2015;195:411–8. doi:10.4049 /jimmunol.1500530.

84. Kaiser S, Rimbach K, Eigenbrod T, Dalpke AH, Helm M. A modified dinucleotide motif specifies tRNA recognition by TLR7. RNA 2014:1351–5. doi:10.1261/rna.044024.113.

85. Jung S, Von Thülen T, Laukemper V, Pigisch S, Hangel D, Wagner H, et al. A single naturally occurring 2’-O-methylation converts a TLR7- and TLR8-activating RNA into a TLR8-specific ligand. PLoS One 2015;10:1–10. doi:10.1371/journal. pone.0120498.

86. Jöckel S, Nees G, Sommer R, Zhao Y, Cherkasov D, Hori H, et al. The 2′- O -methylation status of a single guanosine controls transfer RNA–mediated Toll-like receptor 7 activation or inhibition. J Exp Med 2012;209:235–41. doi:10.1084/jem.20111075.

87. Abdullah Z, Schlee M, Roth S, Mraheil MA, Barchet W, Böttcher J, et al. RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids. EMBO J 2012;31:4153–64. doi:10.1038/emboj. 2012.274.

88. Shahangian A, Chow EK, Tian X, Kang JR, Ghaffari A, Liu SY, et al. Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice. J Clin Invest 2009;119:1910–20. doi:10.1172/JCI35412.

89. Pfeiffer JK, Virgin HW. Transkingdom control of viral infection and immunity in the mammalian intestine. Science (80- ) 2016;351:aad5872-aad5872. doi:10.1126/science.aad5872.

90. Vignola MJ, Kashatus DF, Taylor GA, Counter CM, Valdivia RH. cPLA2 regulates the expression of type I interferons and intracellular immunity to Chlamydia trachomatis. J Biol Chem 2010;285:21625–35. doi:10.1074/jbc.M110.103010.

91. Owen KA, Anderson CJ, Casanova JE. Salmonella suppresses the TRIF-dependent type I interferon response in macrophages. MBio 2016;7:1–15. doi:10.1128/mBio.02051-15.

92. Sionov E, Mayer-Barber KD, Chang YC, Kauffman KD, Eckhaus MA, Salazar AM, et al. Type I IFN Induction via Poly-ICLC Protects Mice against Cryptococcosis. PLoS Pathog 2015;11:1–19. doi:10.1371/journal.ppat.1005040.

93. Mancuso G, Midiri  a., Biondo C, Beninati C, Zummo S, Galbo R, et al. Type I IFN Signaling Is Crucial for Host Resistance against Different Species of Pathogenic Bacteria. J Immunol 2007;178:3126–33. doi:10.4049/jimmunol.178.5.3126.

94. Malireddi RKS, Kanneganti T-D. Role of type I interferons in inflammasome activation, cell death, and disease during microbial infection. Front Cell Infect Microbiol 2013;3:77. doi:10.3389/ fcimb.2013.00077.

95. Rayamajhi M, Humann J, Kearney S, Hill KK, Lenz LL. Antagonistic crosstalk between type I and II interferons and increased host susceptibility to bacterial infections. Virulence 2010;1:418–22. doi:10.4161/viru.1.5.12787.

96. Wiens KE, Ernst JD. The Mechanism for Type I Interferon Induction by Mycobacterium tuberculosis is Bacterial Strain-Dependent. PLoS Pathog 2016;12:1–20. doi:10.1371/journal.ppat.1005809.

97. Petzke MM, Iyer R, Love AC, Spieler Z, Brooks A, Schwartz I. Borrelia burgdorferi induces a type I interferon response during early stages of disseminated infection in mice. BMC Microbiol 2016;16:29. doi:10.1186/s12866-016-0644-4.

98. D’Elios et al. T-cell response to bacterial agents. J Infect Dev Ctries 2011;5:640–5. doi:10.3855/ jidc.2019.

99. Liang SC, Tan X-Y, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006;203:2271–9. doi:10.1084/jem.20061308.

100. Lee B, Robinson KM, McHugh KJ, Scheller E V, Mandalapu S, Chen C, et al. Influenza-induced Type I Interferon Enhances Susceptibility to Gram-negative and Gram-positive Bacterial Pneumonia in Mice. Am J Physiol Lung Cell Mol Physiol 2015:ajplung.00338.2014. doi:10.1152/ajplung. 00338.2014.

101. Kudva A, Scheller E V, Robinson KM, Crowe CR, Choi SM, Slight SR, et al. Influenza A Inhibits Th17-Mediated Host Defense against Bacterial Pneumonia in Mice. J Immunol 2011;186:1666–74. doi:10.4049 /jimmunol.1002194.

102. Li W, Moltedo B, Moran TM. Type I interferon induction during influenza virus infection increases susceptibility to secondary Streptococcus pneumoniae infection by negative regulation of γδ T cells. J Virol 2012;86:12304–12. doi:10.1128/ JVI.01269-12.

103. Unger BL, Ganesan S, Comstock AT, Faris AN, Hershenson MB, Sajjan US. Nod-like receptor X-1 is required for rhinovirus-induced barrier dysfunction in airway epithelial cells. J Virol 2014;88:3705–18. doi:10.1128/JVI.03039-13.

104. Huang L-Y, Stuart C, Takeda K, D’Agnillo F, Golding B, Morita K, et al. Poly(I:C) Induces Human Lung Endothelial Barrier Dysfunction by Disrupting Tight Junction Expression of Claudin-5. PLoS One 2016;11:e0160875. doi:10.1371/journal.pone.0160875.

105. Harper RW, Xu C, Eiserich JP, Chen Y, Kao CY, Thai P, et al. Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium. FEBS Lett 2005;579:4911–7. doi:10.1016/j.febslet. 2005.08.002.

106. Geiszt M. Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J 2003;17:1502–4. doi:10.1096/ fj.02-1104fje.

107. Barraud N, Hassett DJ, Hwang S-H, Rice SA, Kjelleberg S, Webb JS. Involvement of Nitric Oxide in Biofilm Dispersal of Pseudomonas aeruginosa. J Bacteriol 2006;188:7344–53. doi:10.1128/JB.00779-06.

108. Panmanee W, Hassett DJ. Differential roles of OxyR-controlled antioxidant enzymes alkyl hydroperoxide reductase (AhpCF) and catalase (KatB) in the protection of Pseudomonas aeruginosa against hydrogen peroxide in biofilm vs. planktonic culture. FEMS Microbiol Lett 2009;295:238–44. doi:10.1111/j.1574-6968.2009.01605.x.

109. Spoering AL, Lewis K. Biofilms and Planktonic Cells of Pseudomonas aeruginosa Have Similar Resistance to Killing by Antimicrobials. J Bacteriol 2001;183:6746–51. doi:10.1128/JB.183.23.6746-6751.2001.

110. Chattoraj SS, Ganesan S, Jones AM, Helm JM, Comstock AT, Bright-Thomas R, et al. Rhinovirus infection liberates planktonic bacteria from biofilm and increases chemokine responses in cystic fibrosis airway epithelial cells. Thorax 2011;66:333–9. doi:10.1136/thx.2010.151431.

111. Bergstrom B, Aune MH, Awuh J a., Kojen JF, Blix KJ, Ryan L, et al. TLR8 Senses Staphylococcus aureus RNA in Human Primary Monocytes and Macrophages and Induces IFN- Production via a TAK1-IKK -IRF5 Signaling Pathway. J Immunol 2015;195:doi:10.4049/jimmunol.1403176.

112. Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2008;19:92–105. doi:10.1101/gr.082701.108.

113. Hammond SM. An overview of microRNAs. Adv Drug Deliv Rev 2015;87:3–14. doi:10.1016/j.addr. 2015.05.001.

114. Ishikawa H, Otaka H, Maki K, Morita T, Aiba H. The functional Hfq-binding module of bacterial sRNAs consists of a double or single hairpin preceded by a U-rich sequence and followed by a 3’ poly(U) tail. RNA 2012;18:1062–74. doi:10.1261/rna.031575.111.

115. Belter A, Gudanis D, Rolle K, Piwecka M, Gdaniec Z, Naskręt-Barciszewska MZ, et al. Mature miRNAs form secondary structure, which suggests their function beyond RISC. PLoS One 2014;9:1–23. doi:10.1371/journal.pone.0113848.

116. Shabalina SA, Spiridonov NA, Kashina A. Sounds of silence: Synonymous nucleotides as a key to biological regulation and complexity. Nucleic Acids Res 2013;41:2073–94. doi:10.1093/nar/gks1205.

117. Shabalina S a., Koonin E V. Origins and evolution of eukaryotic RNA interference. Trends Ecol Evol 2008;23:578–87. doi:10.1016/j.tree.2008.06.005.

118. Wilusz CJ, Wilusz J. Lsm proteins and Hfq: Life at the 3’ end. RNA Biol 2013;10:592–601. doi:10.4161 /rna.23695.

119. Zhao H, Lii Y, Zhu P, Jin H. Isolation and Profiling of Protein-Associated Small RNAs. In: Jin H, Gassmann W, editors. RNA Abundance Anal. Methods Protoc., Totowa, NJ: Humana Press; 2012, p. 165–76. doi:10.1007/978-1-61779-839-9_13.

120. Zhang H, Li Y, Liu Y, Liu H, Wang H, Jin W, et al. Role of plant MicroRNA in cross-species regulatory networks of humans. BMC Syst Biol 2016;10:60. doi:10.1186/s12918-016-0292-1.

121. Buck AH, Coakley G, Simbari F, McSorley HJ, Quintana JF, Le Bihan T, et al. Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat Commun 2014;5:5488. doi:10.1038/ncomms6488.

122. Lalaouna D, Simoneau-Roy M, Lafontaine D, Massé E. Regulatory RNAs and target mRNA decay in prokaryotes. Biochim Biophys Acta - Gene Regul Mech 2013;1829:742–7. doi:10.1016/j.bbagrm.2013 .02.013.

123. Yates LA, Norbury CJ, Gilbert RJC. The Long and Short of MicroRNA. Cell 2013;153:516–9. doi:10.1016/j.cell.2013.04.003.

124. Shmaryahu A, Carrasco M, Valenzuela PDT. Prediction of Bacterial microRNAs and possible targets in human cell transcriptome. J Microbiol 2014;52:482–9. doi:10.1007/s12275-014-3658-3.

125. Miller WG, Parker CT, Rubenfield M, Mendz GL, Wösten MMSM, Ussery DW, et al. The complete genome sequence and analysis of the epsilonproteobacterium Arcobacter butzleri. PLoS One 2007;2. doi:10.1371/journal.pone.0001358.

126. Grishok A. Biology and Mechanisms of Short RNAs in Caenorhabditis elegans. Adv. Genet., vol. 83, 2013, p. 1–69. doi:10.1016/B978-0-12-407675-4.00001-8.

127. Tang G. A biochemical framework for RNA silencing in plants. Genes Dev 2003;17:49–63. doi:10.1101/gad.1048103.

128. Winston WM, Sutherlin M, Wright AJ, Feinberg EH, Hunter CP. Caenorhabditis elegans SID-2 is required for environmental RNA interference. Proc Natl Acad Sci 2007;104:10565–70. doi:10.1073/pnas.0611282 104.

129. Akay A, Sarkies P, Miska EA. E. coli OxyS non-coding RNA does not trigger RNAi in C. elegans. Sci Rep 2015;5:9597. doi:10.1038/srep09597.

130. Weiberg A, Wang M, Lin F-M, Zhao H, Zhang Z, Kaloshian I, et al. Fungal small RNAs suppress plant immunity by hijacking host RNA interference pathways. Science 2013;342:118–23. doi:10.1126/ science.1239705.

News & Events Latest news from Discoveries

  • 2022, April| AWARDS!

    2022 Discoveries Award winning articles!

    - Kinal Bhatt et al. 2021 (Larking Health System, FL, USA); Bhatt K, Agolli A, Patel MH, et al. High mortality co-infections of COVID-19 patients: mucormycosis and other fungal infections. Discoveries. 2021;9(1):e126. 
    27 citations in the past 1 year - $1000 prize

    - Hasnain Jan et al. 2020 (Quaid-i-Azam University, Pakistan); Jan H, Faisal S, Khan A, et al. COVID-19: Review of Epidemiology and Potential Treatments Against 2019 Novel Coronavirus. Discoveries. 2020;8(2):e108. 
    23 citations in the past 2 years - $400 prize

    Congratulations! Prizes will be received by the awardees in July 2022!

  • 2021, July| 2021, Jul-September

    Due to the high volume of the submitted articles, both Discoveries and Discoveries Reports are experiencing processing and publication delays during the months of July-September 2021. We will get back to the normal processing and publication times starting in October 2021. Note that our editorial and administrativ work is fully funded by our publishing house at this time and we are striving to KEEP THE NO FEE/NO CHARGE strategy in place as long as possible. 

  • 2021, January| AWARDS!

    2022 DISCOVERIES AWARDS! Discoveries will offer $1000 and $400 awards in early 2022, for the most cited (2021 ISI Citations) and visible articles published in 2018-2021.

  • 2020, November| Follow us on Twitter!

    You can now follow the latest Discoveries news and updates on Twitter! (@DiscoveriesNews) 

  • 2020, August| For Authors!

    Due to a high volume of article submissions, our peer-review process takes more than usual. The pre-screening decision is released in 1-2 days, while the peer-review process lasts between 10 and 20 days.  

  • 2020, April | For Authors!

    WE DO NOT TOLERATE ANY MISCONDUCT! Please be aware that we are testing all received articles with specialized software for PLAGIARISM and WE WILL TAKE MEASURES if your article is already published or in consideration for publication by other journals! This may result in serious professional consequences for the authors. The latest striking case is the following article which is already published and was re-submitted here.  

  • 2020, April | For Authors!

    We are happy to let you know that all articles published in Discoveries are now included in PubMedCentral (PMC). New accepted articles will be included in PMC and PubMed within 1-2 weeks after their publication.

  • 2020, January | For Authors!

    Starting in January 2020, Discoveries will also consider articles submitted by Discoveries' Editorial Board members. However, only a small number of such articles (maximum 4 articles/year) will be considered for publication after the peer-review process, and the authors who are also our editors will be clearly disclosed on our website.  

  • 2019, September | Indexed by PMC

    Discoveries is now indexed by PubMedCentral and Pubmed. The agreement with US National Library of Medicine was signed on September 10, 2019. Our next step is ISI Web of Science indexing. NOTE: previously published articles will be included on PubMed in early 2020.

  • 2019, September | PubMed inclusion!

    We are happy to let you know that Discoveries successfuly passed the last step (Technical Review) required for PubMedCentral and PubMed inclusion!

  • 2019, July | PubMed inclusion News!

    We are happy to receive positive comments from PMC/NLM-NIH regarding Discoveries' last step (Technical Review) required for PubMedCentral and PubMed inclusion. We will let you know once whole indexing process is completed. 

  • 2019| Sharing and Distribution!

    All articles published in Discoveries are Open Access articles distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited and it is not used for commercial purposes.

  • 2018-2019 | For Authors!

    From now on and for at least 1 year, we will only accept articles from authors that are NOT members of Discoveries' Editorial Board. All articles submitted by our editors will be immediately rejected until further notice (one accepted article was already rejected). 

  • 2018 | PubMed inclusion News!

    Discoveries successfully passed the Scientific Quality Review by NLM-NIH for PubMedCentral and PubMed indexing. This is the first and the most important step towards PubMedCentral and PubMed indexing! The second (last) step is the Technical Review.

  • 2016, April | Faster Peer-Review

    Starting on April 13th 2016, all articles selected for a peer-review will receive the post peer-review decision within ~10 days. The initial pre-screening time will remain the same (48h from the submission of the manuscript). This decision will significantly accelerate the publication, with no effect on the quality of the peer-review process.

  • 2016, February | Manuscript submission

    Discoveries is commited to excellence, quality and high editorial standards. We are receiving an increasing number of manuscripts for which the identity of the authors/corresponding author can't be verified. Please NOTE that ALL these articles were and will be immediately REJECTED. Indicating an institutional email address is the easiest way to overcome this problem! Moreover, we do not accept any pressure on our editorial board to accept a manuscript. This results in a prompt rejection of the article.

    Editorial Policies
  • 2016, January | Main Objective

    After reaching all proposed milestones until now (including being indexed by Google Scholar in 2014), Discoveries' next Aim is PubMed indexing of all its articles (already published and upcoming). There will be no charge for the submission or publication of articles before Discoveries is indexed.

  • 2015, August | Discoveries - on PubMed

    We are happy to announce that our first Discoveries articles were included in PMC and PubMed. More articles (submitted by NIH funded authors) are now processed for being included.

    Discoveries articles now on PubMed
  • 2015, April | Special Issue

    DISCOVERIES published the SPECIAL ISSUE entitled "INFLAMMATION BETWEEN DEFENSE AND DISEASE: Impact on Tissue Repair and Chronic Sickness".

    Special Issue on "Inflammation"
  • 2015 | Ischemia Collection

    DISCOVERIES launched a call for papers for a Collection of Articles with focus on "ISCHEMIA". If you are interested to submit a manuscript, please contact us at info@discoveriesjournals.org

  • 2014, September | Special Issue

    DISCOVERIES just publish the SPECIAL ISSUE entitled "CELL SECRETION & MEMBRANE FUSION" in September 2014. Initially scheduled for publication between October 2014-March 2015, this issue was successfully published earlier than scheduled. 

    Special Issue
  • 2014, April | Indexed by Google Scholar

    All our published articles are now indexed by Google Scholar! First citations to Discoveries articles are included! Search for the article's title (recommended) or the authors:

    Google Scholar Search
  • 2014 | DISCOVERIES

    DOIs (Digital Object Identifiers) are now assigned to all our published manuscripts in Discoveries. DOI uniquely identifies an article and is provided by CrossRef.

  • 2013, July | Manuscript Submission

    Submit your manuscript FREE, FAST and EASY ! (in less than 1 minute)! There are NO fees for the manuscript submission or publishing of the accepted manuscripts.
    read more

  • 2013, July | DISCOVERIES

    We are now ACCEPTING MANUSCRIPTS for publishing in DISCOVERIES. We aim publishing a small number of high impact experimental articles & reviews (around 40/year) to maintain a high impact factor. Domains of interest: all areas related to Medicine, Biology and Chemistry ...

    read more
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