{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:43:47Z","timestamp":1790696627266,"version":"4.1.0"},"reference-count":117,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T00:00:00Z","timestamp":1478131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1047635"],"award-info":[{"award-number":["1047635"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Influenza remains a major global health issue and the effectiveness of current vaccines and antiviral drugs is limited by the continual evolution of influenza viruses. Therefore, identifying novel prophylactic or therapeutic treatments that induce appropriate innate immune responses to protect against influenza infection would represent an important advance in efforts to limit the impact of influenza. Cellular pattern recognition receptors (PRRs) recognize conserved structures expressed by pathogens to trigger intracellular signaling cascades, promoting expression of proinflammatory molecules and innate immunity. Therefore, a number of approaches have been developed to target specific PRRs in an effort to stimulate innate immunity and reduce disease in a variety of settings, including during influenza infections. Herein, we discuss progress in immunomodulation strategies designed to target cell-associated PRRs of the innate immune system, thereby, modifying innate responses to IAV infection and\/or augmenting immune responses to influenza vaccines.<\/jats:p>","DOI":"10.1189\/jlb.4mr0716-290r","type":"journal-article","created":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T02:28:59Z","timestamp":1478226539000},"page":"851-861","source":"Crossref","is-referenced-by-count":26,"title":["Pattern recognition receptor immunomodulation of innate immunity as a strategy to limit the impact of influenza virus"],"prefix":"10.1093","volume":"101","author":[{"given":"Angela","family":"Pizzolla","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery M","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C","family":"Reading","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne , Melbourne, Victoria , Australia"},{"name":"The WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,11,3]]},"reference":[{"key":"2023011712061903400_B1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1128\/mr.56.1.152-179.1992","article-title":"Evolution and ecology of influenza A viruses","volume":"56","author":"Webster","year":"1992","journal-title":"Microbiol. Rev."},{"key":"2023011712061903400_B2","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S0140-6736(05)67338-2","article-title":"Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern","volume":"366","author":"Bright","year":"2005","journal-title":"Lancet"},{"key":"2023011712061903400_B3","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3201\/eid1504.181280","article-title":"Oseltamivirresistant influenza virus A (H1N1), Europe, 2007-08 season","volume":"15","author":"Meijer","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"2023011712061903400_B4","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.micinf.2011.01.014","article-title":"The contribution of animal models to the understanding of the host range and virulence of influenza A viruses","volume":"13","author":"O\u2019Donnell","year":"2011","journal-title":"Microbes Infect."},{"key":"2023011712061903400_B5","doi-asserted-by":"crossref","first-page":"e4176","DOI":"10.1371\/journal.pone.0004176","article-title":"Augmented lung inflammation protects against influenza A pneumonia","volume":"4","author":"Tuvim","year":"2009","journal-title":"PLoS One"},{"key":"2023011712061903400_B6","doi-asserted-by":"crossref","first-page":"8680","DOI":"10.1128\/JVI.05142-11","article-title":"Parasite-mediated upregulation of NK cell-derived gamma interferon protects against severe highly pathogenic H5N1 influenza virus infection","volume":"85","author":"O\u2019Brien","year":"2011","journal-title":"J. Virol."},{"key":"2023011712061903400_B7","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/BF02908284","article-title":"Viral interference and interferon","volume":"5","author":"Dianzani","year":"1975","journal-title":"Ric. Clin. Lab."},{"key":"2023011712061903400_B8","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"2023011712061903400_B9","doi-asserted-by":"crossref","first-page":"920","DOI":"10.3390\/v3060920","article-title":"Pattern recognition receptors and the innate immune response to viral infection","volume":"3","author":"Thompson","year":"2011","journal-title":"Viruses"},{"key":"2023011712061903400_B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clim.2013.12.003","article-title":"Airway epithelial regulation of pulmonary immune homeostasis and inflammation","volume":"151","author":"Hallstrand","year":"2014","journal-title":"Clin. Immunol."},{"key":"2023011712061903400_B11","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cyto.2015.07.002","article-title":"The catcher in the RIG-I","volume":"76","author":"Weber","year":"2015","journal-title":"Cytokine"},{"key":"2023011712061903400_B12","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.coviro.2015.01.004","article-title":"RIG-I-like receptor regulation in virus infection and immunity","volume":"12","author":"Chan","year":"2015","journal-title":"Curr. Opin. Virol."},{"key":"2023011712061903400_B13","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1126\/science.1132505","article-title":"5\u2019-Triphosphate RNA is the ligand for RIG-I","volume":"314","author":"Hornung","year":"2006","journal-title":"Science"},{"key":"2023011712061903400_B14","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nri3452","article-title":"Activation and regulation of the inflammasomes","volume":"13","author":"Latz","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"2023011712061903400_B15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tim.2014.09.007","article-title":"Response of host inflammasomes to viral infection","volume":"23","author":"Chen","year":"2015","journal-title":"Trends Microbiol."},{"key":"2023011712061903400_B16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrmicro2070","article-title":"Pyroptosis: host cell death and inflammation","volume":"7","author":"Bergsbaken","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"2023011712061903400_B17","doi-asserted-by":"crossref","first-page":"5354","DOI":"10.1073\/pnas.1019378108","article-title":"Microbiota regulates immune defense against respiratory tract influenza A virus infection","volume":"108","author":"Ichinohe","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023011712061903400_B18","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nri3665","article-title":"Innate immunity to influenza virus infection","volume":"14","author":"Iwasaki","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"2023011712061903400_B19","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1128\/JVI.02200-10","article-title":"Viral replication and innate host responses in primary human alveolar epithelial cells and alveolar macrophages infected with influenza H5N1 and H1N1 viruses","volume":"85","author":"Yu","year":"2011","journal-title":"J. Virol."},{"key":"2023011712061903400_B20","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1465-9921-10-102","article-title":"Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells","volume":"10","author":"Chan","year":"2009","journal-title":"Respir. Res."},{"key":"2023011712061903400_B21","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1099\/vir.0.045021-0","article-title":"The fate of influenza A virus after infection of human macrophages and dendritic cells","volume":"93","author":"Short","year":"2012","journal-title":"J. Gen. Virol."},{"key":"2023011712061903400_B22","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1007\/s13238-015-0191-z","article-title":"Induction of innate immunity and its perturbation by influenza viruses","volume":"6","author":"Goraya","year":"2015","journal-title":"Protein Cell"},{"key":"2023011712061903400_B23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.coi.2016.05.016","article-title":"Standing on three legs: antiviral activities of RIG-I against influenza viruses","volume":"42","author":"Weber-Gerlach","year":"2016","journal-title":"Curr. Opin. Immunol."},{"key":"2023011712061903400_B24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nri3581","article-title":"Regulation of type I interferon responses","volume":"14","author":"Ivashkiv","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"2023011712061903400_B25","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.micinf.2011.01.007","article-title":"Immunity to seasonal and pandemic influenza A viruses","volume":"13","author":"Valkenburg","year":"2011","journal-title":"Microbes Infect."},{"key":"2023011712061903400_B26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/cmi.2015.74","article-title":"The cytokine storm of severe influenza and development of immunomodulatory therapy","volume":"13","author":"Liu","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"2023011712061903400_B27","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1146\/annurev-physiol-021115-105238","article-title":"The microbiome and the respiratory tract","volume":"78","author":"Dickson","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"2023011712061903400_B28","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2174\/1874285801509010167","article-title":"The murine lung microbiome changes during lung inflammation and intranasal vancomycin treatment","volume":"9","author":"Barfod","year":"2015","journal-title":"Open Microbiol. J."},{"key":"2023011712061903400_B29","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1038\/ncomms3106","article-title":"Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages","volume":"4","author":"Wang","year":"2013","journal-title":"Nat. Commun."},{"key":"2023011712061903400_B30","first-page":"1525","article-title":"JTD special edition \u2018hot topics in COPD\u2019\u2014the microbiome in COPD","volume":"6","author":"Chambers","year":"2014","journal-title":"J. Thorac. Dis."},{"key":"2023011712061903400_B31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/mi.2011.55","article-title":"Pulmonary-intestinal crosstalk in mucosal inflammatory disease","volume":"5","author":"Keely","year":"2012","journal-title":"Mucosal Immunol."},{"key":"2023011712061903400_B32","doi-asserted-by":"crossref","first-page":"27870","DOI":"10.1038\/srep27870","article-title":"Nasal commensal Staphylococcus epidermidis counteracts influenza virus","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"2023011712061903400_B33","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1128\/JVI.01805-09","article-title":"Prophylactic administration of bacterially derived immunomodulators improves the outcome of influenza virus infection in a murine model","volume":"84","author":"Norton","year":"2010","journal-title":"J. Virol."},{"key":"2023011712061903400_B34","doi-asserted-by":"crossref","first-page":"7435","DOI":"10.4049\/jimmunol.173.12.7435","article-title":"Innate imprinting by the modified heat-labile toxin of Escherichia coli (LTK63) provides generic protection against lung infectious disease","volume":"173","author":"Williams","year":"2004","journal-title":"J. Immunol."},{"key":"2023011712061903400_B35","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1021\/mp300257x","article-title":"Intranasal administration of the TLR2 agonist Pam2Cys provides rapid protection against influenza in mice","volume":"9","author":"Tan","year":"2012","journal-title":"Mol. Pharm."},{"key":"2023011712061903400_B36","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/icb.2015.81","article-title":"Mapping the pulmonary environment of animals protected from virulent H1N1 influenza infection using the TLR-2 agonist PamCys","volume":"94","author":"Mifsud","year":"2015","journal-title":"Immunol. Cell Biol."},{"key":"2023011712061903400_B37","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1743-422X-8-97","article-title":"Toll-like receptor prestimulation protects mice against lethal infection with highly pathogenic influenza viruses","volume":"8","author":"Shinya","year":"2011","journal-title":"Virol. J."},{"key":"2023011712061903400_B38","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.antiviral.2011.09.004","article-title":"FimH, a TLR4 ligand, induces innate antiviral responses in the lung leading to protection against lethal influenza infection in mice","volume":"92","author":"Abdul-Careem","year":"2011","journal-title":"Antiviral Res."},{"key":"2023011712061903400_B39","doi-asserted-by":"crossref","first-page":"e1000233","DOI":"10.1371\/journal.ppat.1000233","article-title":"FimH adhesin of type 1 fimbriae is a potent inducer of innate antimicrobial responses which requires TLR4 and type 1 interferon signalling","volume":"4","author":"Ashkar","year":"2008","journal-title":"PLoS Pathog."},{"key":"2023011712061903400_B40","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/mt.2010.75","article-title":"FimH can directly activate human and murine natural killer cells via TLR4","volume":"18","author":"Mian","year":"2010","journal-title":"Mol. Ther."},{"key":"2023011712061903400_B41","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1016\/j.molimm.2008.02.001","article-title":"TLR4\/CD14-mediated PI3K activation is an essential component of interferon-dependent VSV resistance in macrophages","volume":"45","author":"Schabbauer","year":"2008","journal-title":"Mol. Immunol."},{"key":"2023011712061903400_B42","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1128\/IAI.73.5.3044-3052.2005","article-title":"Synthetic toll-like receptor 4 agonists stimulate innate resistance to infectious challenge","volume":"73","author":"Cluff","year":"2005","journal-title":"Infect. Immun."},{"key":"2023011712061903400_B43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cell.2008.02.043","article-title":"Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury","volume":"133","author":"Imai","year":"2008","journal-title":"Cell"},{"key":"2023011712061903400_B44","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature12118","article-title":"The TLR4 antagonist Eritoran protects mice from lethal influenza infection","volume":"497","author":"Shirey","year":"2013","journal-title":"Nature"},{"key":"2023011712061903400_B45","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/ni.2767","article-title":"The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids","volume":"15","author":"Agudo","year":"2014","journal-title":"Nat. Immunol."},{"key":"2023011712061903400_B46","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1016\/j.vaccine.2009.01.048","article-title":"Activation of toll-like receptor signaling pathway for protection against influenza virus infection","volume":"27","author":"Wong","year":"2009","journal-title":"Vaccine"},{"key":"2023011712061903400_B47","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1099\/vir.0.19029-0","article-title":"An immunostimulatory oligodeoxynucleotide containing a cytidineguanosine motif protects senescence-accelerated mice from lethal influenza virus by augmenting the T helper type 1 response","volume":"84","author":"Dong","year":"2003","journal-title":"J. Gen. Virol."},{"key":"2023011712061903400_B48","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1016\/j.vaccine.2005.01.037","article-title":"Prophylaxis of acute respiratory virus infections using nucleic acid-based drugs","volume":"23","author":"Wong","year":"2005","journal-title":"Vaccine"},{"key":"2023011712061903400_B49","doi-asserted-by":"crossref","first-page":"e30596","DOI":"10.1371\/journal.pone.0030596","article-title":"Synergistic TLR2\/6 and TLR9 activation protects mice against lethal influenza pneumonia","volume":"7","author":"Tuvim","year":"2012","journal-title":"PLoS One"},{"key":"2023011712061903400_B50","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/nm1589","article-title":"Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists","volume":"13","author":"Kanzler","year":"2007","journal-title":"Nat. Med."},{"key":"2023011712061903400_B51","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1164\/rccm.200601-057OC","article-title":"Immunostimulatory sequences regulate interferon-inducible genes but not allergic airway responses","volume":"174","author":"Gauvreau","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2023011712061903400_B52","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/0264-410X(89)90192-8","article-title":"Protection against influenza virus infection by a two-dose regimen of nasal vaccination using vaccines combined with cholera toxin B subunit","volume":"7","author":"Tamura","year":"1989","journal-title":"Vaccine"},{"key":"2023011712061903400_B53","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/0264-410X(94)90118-X","article-title":"Synergistic action of cholera toxin B subunit (and Escherichia coli heat-labile toxin B subunit) and a trace amount of cholera whole toxin as an adjuvant for nasal influenza vaccine","volume":"12","author":"Tamura","year":"1994","journal-title":"Vaccine"},{"key":"2023011712061903400_B54","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1016\/S0264-410X(00)00412-6","article-title":"Effects of intranasal administration of cholera toxin (or Escherichia coli heat-labile enterotoxin) B subunits supplemented with a trace amount of the holotoxin on the brain.) Effects of intranasal administration of cholera toxin (or Escherichia coli heat-labile enterotoxin) B subunits supplemented with a trace amount of the holotoxin on the brain","volume":"19","author":"Hagiwara","year":"2001","journal-title":"Vaccine"},{"key":"2023011712061903400_B55","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.coi.2014.01.009","article-title":"Challenges and responses in human vaccine development","volume":"28","author":"Kaufmann","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"2023011712061903400_B56","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1016\/j.vaccine.2013.08.064","article-title":"Evaluation of safety and immunogenicity of recombinant influenza hemagglutinin (H5\/Indonesia\/05\/2005) formulated with and without a stable oil-inwater emulsion containing glucopyranosyl-lipid A (SE+GLA) adjuvant","volume":"31","author":"Treanor","year":"2013","journal-title":"Vaccine"},{"key":"2023011712061903400_B57","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1093\/infdis\/jir769","article-title":"GLA-SE, a synthetic toll-like receptor 4 agonist, enhances T-cell responses to influenza vaccine in older adults","volume":"205","author":"Behzad","year":"2012","journal-title":"J. Infect. Dis."},{"key":"2023011712061903400_B58","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1016\/j.vaccine.2004.01.058","article-title":"Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine","volume":"22","author":"Cooper","year":"2004","journal-title":"Vaccine"},{"key":"2023011712061903400_B59","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1016\/j.vaccine.2008.04.029","article-title":"The novel adjuvant IC31 strongly improves influenza vaccine-specific cellular and humoral immune responses in young adult and aged mice","volume":"26","author":"Riedl","year":"2008","journal-title":"Vaccine"},{"key":"2023011712061903400_B60","doi-asserted-by":"crossref","first-page":"15440","DOI":"10.1073\/pnas.0406740101","article-title":"A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses","volume":"101","author":"Jackson","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023011712061903400_B61","doi-asserted-by":"crossref","first-page":"e01024","DOI":"10.1128\/mBio.01024-15","article-title":"Inactivated influenza vaccine that provides rapid, innate-immune-system-mediated protection and subsequent long-term adaptive immunity","volume":"6","author":"Chua","year":"2015","journal-title":"MBio"},{"key":"2023011712061903400_B62","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/0264-410X(92)90071-Q","article-title":"Synthetic recombinant vaccine expressing influenza haemagglutinin epitope in Salmonella flagellin leads to partial protection in mice","volume":"10","author":"McEwen","year":"1992","journal-title":"Vaccine"},{"key":"2023011712061903400_B63","doi-asserted-by":"crossref","first-page":"5875","DOI":"10.1016\/j.vaccine.2009.07.060","article-title":"Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin","volume":"27","author":"Song","year":"2009","journal-title":"Vaccine"},{"key":"2023011712061903400_B64","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.vaccine.2007.10.062","article-title":"Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin","volume":"26","author":"Huleatt","year":"2008","journal-title":"Vaccine"},{"key":"2023011712061903400_B65","doi-asserted-by":"crossref","first-page":"5761","DOI":"10.1016\/j.vaccine.2012.06.086","article-title":"Development of VAX128, a recombinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response","volume":"30","author":"Taylor","year":"2012","journal-title":"Vaccine"},{"key":"2023011712061903400_B66","doi-asserted-by":"crossref","first-page":"5145","DOI":"10.1016\/j.vaccine.2011.05.041","article-title":"Safety and immunogenicity of a recombinant M2e-flagellin influenza vaccine (STF2.4xM2e) in healthy adults","volume":"29","author":"Turley","year":"2011","journal-title":"Vaccine"},{"key":"2023011712061903400_B67","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.immuni.2014.08.009","article-title":"TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination","volume":"41","author":"Oh","year":"2014","journal-title":"Immunity"},{"key":"2023011712061903400_B68","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.immuni.2014.10.005","article-title":"SnapShot: nucleic acid immune sensors, part 1","volume":"41","author":"Hornung","year":"2014","journal-title":"Immunity"},{"key":"2023011712061903400_B69","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.immuni.2014.10.006","article-title":"SnapShot: Nucleic acid immune sensors, part 2","volume":"41","author":"Hornung","year":"2014","journal-title":"Immunity"},{"key":"2023011712061903400_B70","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.2174\/138161209787846775","article-title":"Antiviral role of toll-like receptor-3 agonists against seasonal and avian influenza viruses","volume":"15","author":"Wong","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"2023011712061903400_B71","doi-asserted-by":"crossref","first-page":"11416","DOI":"10.1128\/JVI.01410-12","article-title":"Intranasal treatment with poly (I\u2022C) protects aged mice from lethal respiratory virus infections","volume":"86","author":"Zhao","year":"2012","journal-title":"J. Virol."},{"key":"2023011712061903400_B72","doi-asserted-by":"crossref","first-page":"a016246","DOI":"10.1101\/cshperspect.a016246","article-title":"Microbial sensing by Toll-like receptors and intracellular nucleic acid sensors","volume":"7","author":"Pandey","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2023011712061903400_B73","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/ni1087","article-title":"The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses","volume":"5","author":"Yoneyama","year":"2004","journal-title":"Nat. Immunol."},{"key":"2023011712061903400_B74","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1126\/science.1093620","article-title":"Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8","volume":"303","author":"Heil","year":"2004","journal-title":"Science"},{"key":"2023011712061903400_B75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2006.07.011","article-title":"Administration of a dual toll-like receptor 7 and toll-like receptor 8 agonist protects against influenza in rats","volume":"73","author":"Hammerbeck","year":"2007","journal-title":"Antiviral Res."},{"key":"2023011712061903400_B76","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1159\/000355217","article-title":"Innate immune protection against infectious diseases by pulmonary administration of a phospholipidconjugated TLR7 ligand","volume":"6","author":"Wu","year":"2014","journal-title":"J. Innate Immun."},{"key":"2023011712061903400_B77","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nbt1081","article-title":"Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA","volume":"23","author":"Judge","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"2023011712061903400_B78","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nm1191","article-title":"Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7","volume":"11","author":"Hornung","year":"2005","journal-title":"Nat. Med."},{"key":"2023011712061903400_B79","doi-asserted-by":"crossref","first-page":"8676","DOI":"10.1073\/pnas.0402486101","article-title":"Inhibition of influenza virus production in virus-infected mice by RNA interference","volume":"101","author":"Ge","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023011712061903400_B80","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1073\/pnas.0437841100","article-title":"RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription","volume":"100","author":"Ge","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023011712061903400_B81","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1007\/s00705-011-1087-8","article-title":"Inhibition of influenza A virus replication by RNA interference targeted against the PB1 subunit of the RNA polymerase gene","volume":"156","author":"Li","year":"2011","journal-title":"Arch. Virol."},{"key":"2023011712061903400_B82","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1089\/nat.2012.0359","article-title":"Small interfering RNA targeting the nonstructural gene 1 transcript inhibits influenza A virus replication in experimental mice","volume":"22","author":"Rajput","year":"2012","journal-title":"Nucleic Acid Ther."},{"key":"2023011712061903400_B83","doi-asserted-by":"crossref","first-page":"8682","DOI":"10.1073\/pnas.0402630101","article-title":"Protection against lethal influenza virus challenge by RNA interference in vivo","volume":"101","author":"Tompkins","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023011712061903400_B84","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1089\/hum.2008.131","article-title":"Misinterpreting the therapeutic effects of small interfering RNA caused by immune stimulation","volume":"19","author":"Robbins","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"2023011712061903400_B85","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1038\/mt.2009.147","article-title":"Drug delivery-mediated control of RNA immunostimulation","volume":"17","author":"Nguyen","year":"2009","journal-title":"Mol. Ther."},{"key":"2023011712061903400_B86","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/icb.2011.19","article-title":"siRNA-induced immunostimulation through TLR7 promotes antitumoral activity against HPV-driven tumors in vivo","volume":"90","author":"Khairuddin","year":"2012","journal-title":"Immunol. Cell Biol."},{"key":"2023011712061903400_B87","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1007\/s11095-008-9766-1","article-title":"Development of a novel method for formulating stable siRNA-loaded lipid particles for in vivo use","volume":"26","author":"Wu","year":"2009","journal-title":"Pharm. Res."},{"key":"2023011712061903400_B88","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1038\/mtna.2013.22","article-title":"Efficient biodistribution and gene silencing in the lung epithelium via intravenous liposomal delivery of siRNA","volume":"2","author":"McCaskill","year":"2013","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"2023011712061903400_B89","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.virusres.2015.02.003","article-title":"Influenza virus activation of the interferon system","volume":"209","author":"Killip","year":"2015","journal-title":"Virus Res."},{"key":"2023011712061903400_B90","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.immuni.2009.05.008","article-title":"Recognition of 5\u2019 triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus","volume":"31","author":"Schlee","year":"2009","journal-title":"Immunity"},{"key":"2023011712061903400_B91","doi-asserted-by":"crossref","first-page":"12067","DOI":"10.1073\/pnas.0900971106","article-title":"5\u2019-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I","volume":"106","author":"Schmidt","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023011712061903400_B92","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1743-422X-7-102","article-title":"5\u2019PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication","volume":"7","author":"Ranjan","year":"2010","journal-title":"Virol. J."},{"key":"2023011712061903400_B93","doi-asserted-by":"crossref","first-page":"e1003298","DOI":"10.1371\/journal.ppat.1003298","article-title":"Systems analysis of a RIG-I agonist inducing broad spectrum inhibition of virus infectivity [published correction in PLoS Pathog. (2013) 9, doi: 10.1371\/annotation\/8fa70b21-32e7-4ed3-b397-ab776b5bbf30.]","volume":"9","author":"Goulet","year":"2013","journal-title":"PLoS Pathog."},{"key":"2023011712061903400_B94","doi-asserted-by":"crossref","first-page":"8011","DOI":"10.1128\/JVI.00845-15","article-title":"Sequence-specific modifications enhance the broad-spectrum antiviral response activated by RIG-I agonists","volume":"89","author":"Chiang","year":"2015","journal-title":"J. Virol."},{"key":"2023011712061903400_B95","doi-asserted-by":"crossref","first-page":"10359","DOI":"10.1128\/JVI.00665-12","article-title":"5\u2019-Triphosphate-short interfering RNA: potent inhibition of influenza A virus infection by gene silencing and RIG-I activation","volume":"86","author":"Lin","year":"2012","journal-title":"J. Virol."},{"key":"2023011712061903400_B96","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1128\/JVI.79.5.2910-2919.2005","article-title":"Synthetic double-stranded RNA poly(I:C) combined with mucosal vaccine protects against influenza virus infection","volume":"79","author":"Ichinohe","year":"2005","journal-title":"J. Virol."},{"key":"2023011712061903400_B97","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1016\/j.vaccine.2009.01.071","article-title":"Ampligen: a potential toll-like 3 receptor adjuvant for immunotherapy of cancer","volume":"27","author":"Jasani","year":"2009","journal-title":"Vaccine"},{"key":"2023011712061903400_B98","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1128\/AAC.39.11.2574","article-title":"Prophylactic and therapeutic efficacies of poly(IC\u2022LC) against respiratory influenza A virus infection in mice","volume":"39","author":"Wong","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"2023011712061903400_B99","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.vaccine.2008.12.048","article-title":"A TLR3 ligand that exhibits potent inhibition of influenza virus replication and has strong adjuvant activity has the potential for dual applications in an influenza pandemic","volume":"27","author":"Lau","year":"2009","journal-title":"Vaccine"},{"key":"2023011712061903400_B100","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.4049\/jimmunol.1002845","article-title":"TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection","volume":"186","author":"Jelinek","year":"2011","journal-title":"J. Immunol."},{"key":"2023011712061903400_B101","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.4049\/jimmunol.1400222","article-title":"Mucosal polyinosinic-polycytidylic acid improves protection elicited by replicating influenza vaccines via enhanced dendritic cell function and T cell immunity","volume":"193","author":"P\u00e9rez-Gir\u00f3n","year":"2014","journal-title":"J. Immunol."},{"key":"2023011712061903400_B102","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/jmv.21694","article-title":"Zymosan enhances the mucosal adjuvant activity of poly(I:C) in a nasal influenza vaccine","volume":"82","author":"Ainai","year":"2010","journal-title":"J. Med. Virol."},{"key":"2023011712061903400_B103","first-page":"640","article-title":"Phase I trials of poly(I,C) complexes in advanced cancer","volume":"4","author":"Krown","year":"1985","journal-title":"J. Biol. Response Mod."},{"key":"2023011712061903400_B104","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s11060-008-9693-3","article-title":"A phase II clinical trial of poly-ICLC with radiation for adult patients with newly diagnosed supratentorial glioblastoma: a North American Brain Tumor Consortium (NABTC01-05)","volume":"91","author":"Butowski","year":"2009","journal-title":"J. Neurooncol."},{"key":"2023011712061903400_B105","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1200\/JCO.2010.30.7744","article-title":"Induction of CD8+ T-cell responses against novel gliomaassociated antigen peptides and clinical activity by vaccinations with alpha-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma","volume":"29","author":"Okada","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"2023011712061903400_B106","volume-title":"Immunogenic Substances Comprising a Polyinosinic Acid\u2013Polycytidilic Acid Based Adjuvant","author":"Lin","year":"2012"},{"key":"2023011712061903400_B107","author":"Yisheng Biopharma Co., Ltd","year":"2015"},{"key":"2023011712061903400_B108","doi-asserted-by":"crossref","first-page":"27912","DOI":"10.1038\/srep27912","article-title":"Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition","volume":"6","author":"Tate","year":"2016","journal-title":"Sci. Rep."},{"key":"2023011712061903400_B109","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.immuni.2012.04.011","article-title":"Commensal bacteria calibrate the activation threshold of innate antiviral immunity","volume":"37","author":"Abt","year":"2012","journal-title":"Immunity"},{"key":"2023011712061903400_B110","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nature06939","article-title":"Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants","volume":"453","author":"Eisenbarth","year":"2008","journal-title":"Nature"},{"key":"2023011712061903400_B111","doi-asserted-by":"crossref","first-page":"9081","DOI":"10.1016\/j.vaccine.2011.09.051","article-title":"Adjuvants that stimulate TLR3 or NLPR3 pathways enhance the efficiency of influenza virus-like particle vaccines in aged mice","volume":"29","author":"Schneider-Ohrum","year":"2011","journal-title":"Vaccine"},{"key":"2023011712061903400_B112","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1089\/oli.2009.0180","article-title":"siRNA and innate immunity","volume":"19","author":"Robbins","year":"2009","journal-title":"Oligonucleotides"},{"key":"2023011712061903400_B113","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0378-1135(00)00171-1","article-title":"Cytokines in the pathogenesis of influenza","volume":"74","author":"Van Reeth","year":"2000","journal-title":"Vet. Microbiol."},{"key":"2023011712061903400_B114","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.3390\/v20801530","article-title":"Animal models for influenza virus pathogenesis and transmission","volume":"2","author":"Bouvier","year":"2010","journal-title":"Viruses"},{"key":"2023011712061903400_B115","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1165\/rcmb.2006-0330OC","article-title":"Long-term deposition of inhaled antigen in lung resident CD11b-CD11c+ cells","volume":"36","author":"Matthews","year":"2007","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2023011712061903400_B116","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1741-7015-10-104","article-title":"New treatments for influenza","volume":"10","author":"Barik","year":"2012","journal-title":"BMC Med."},{"key":"2023011712061903400_B117","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nbt.1542","article-title":"MicroRNA-mediated species-specific attenuation of influenza A virus","volume":"27","author":"Perez","year":"2009","journal-title":"Nat. Biotechnol."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/101\/4\/851\/48718514\/jlb0851.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/101\/4\/851\/48718514\/jlb0851.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T13:36:12Z","timestamp":1677504972000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/101\/4\/851\/6932955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,3]]},"references-count":117,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,11,3]]},"published-print":{"date-parts":[[2017,4,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.4mr0716-290r","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,4]]},"published":{"date-parts":[[2016,11,3]]}}}