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Review

Innate immunity to influenza virus: implications for future therapy

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Pages 497-514 | Published online: 10 Jan 2014

References

  • Morens DM. Influenza-related mortality. JAMA289, 227–229 (2003).
  • Garcia-Sastre A, Whitley RJ. Lessons learned from reconstructing the 1918 influenza pandemic. J. Infect. Dis.194(Suppl. 2), S127–S132 (2006).
  • Finberg RW, Wang JP, Kurt-Jones EA. Toll like receptors and viruses. Rev. Med. Virol.17(1), 35–43 (2007).
  • Hartshorn KL, Ligtenberg A, White MR et al. Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation. Biochemistry393, 545–553 (2006).
  • Hartshorn KL, White MR, Mogues T et al. Lung and salivary scavenger receptor glycoprotein-340 contribute to the host defense against influenza A viruses. Am. J. Physiol. Lung Cell. Mol. Physiol.285(5), L1066–L1076 (2003).
  • Brauer L, Kindler C, Jager K et al. Detection of surfactant proteins A and D in human tear fluid and the human lacrimal system. Invest. Ophthalmol. Vis. Sci.48(9), 3945–3953 (2007).
  • Belser JA, Lu X, Maines TR et al. Pathogenesis of avian influenza (H7) virus infection in mice and ferrets: enhanced virulence of Eurasian H7N7 viruses isolated from humans. J. Virol.81(20), 11139–11147 (2007).
  • Reading PC, Bozza S, Gilbertson B et al. Antiviral activity of the long chain pentraxin PTX3 against influenza viruses. J. Immunol.180(5), 3391–3398 (2008).
  • White MR, Crouch E, van Eijk M et al. Cooperative anti-influenza activities of respiratory innate immune proteins and neuraminidase inhibitor. Am. J. Physiol. Lung Cell. Mol. Physiol.288(5), L831–L840 (2005).
  • White MR, Crouch E, Vesona J et al. Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus. Am. J. Physiol. Lung Cell. Mol. Physiol.289(4), L606–L616 (2005).
  • Kuroki Y, Takahashi M, Nishitani C. Pulmonary collectins in innate immunity of the lung. Cell. Microbiol.9(8), 1871–1879 (2007).
  • Whitsett JA. Surfactant proteins in innate host defense of the lung. Biol. Neonate88(3), 175–180 (2005).
  • Hartshorn KL, Crouch EC, White MR et al. Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J. Clin. Invest.94, 311–319 (1994).
  • Madsen J, Kliem A, Tornoe I et al. Localization of lung surfactant protein D on mucosal surfaces in human tissues. J. Immunol.164, 5866–5870 (2000).
  • LeVine AM, Whitsett JA, Hartshorn KL, Crouch EC, Korfhagen TR. Surfactant protein D enhances clearance of influenza A virus from the lung in vivo.J. Immunol.167(10), 5868–5873 (2001).
  • Hawgood S, Brown C, Edmondson J et al. Pulmonary collectins modulate strain-specific influenza A virus infection and host responses. J. Virol.78(16), 8565–8572 (2004).
  • Kingma PS, Zhang L, Ikegami M et al. Correction of pulmonary abnormalities in Sftpd-/- mice requires the collagenous domain of surfactant protein D. J. Biol. Chem.281(34), 24496–24505 (2006).
  • Zhang L, Hartshorn K, Crouch E, Ikegami M, Whitsett J. Complementation of pulmonary abnormalities in SP-D-/- mice with an SP-D/conglutinin fusion protein. J. Biol. Chem.277, 22453–22459 (2002).
  • Reading P, Morey L, Crouch E, Anders E. Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. J. Virol.71, 8204–8212 (1997).
  • Hartley C, Reading P, Ward A, Anders E. Changes in hemagglutinin molecule of influenza type A (H3N2) virus associated with increased virulence in mice. Arch. Virol.142, 75–88 (1997).
  • Hartshorn KL, Sastry K, White MR et al. Human mannose-binding protein functions as an opsonin for influenza A viruses. J. Clin. Invest.91, 1414–1420 (1993).
  • Vigerust DJ, Ulett KB, Boyd KL et al. N-linked glycosylation attenuates H3N2 influenza viruses. J. Virol.81(16), 8593–8600 (2007).
  • Stevens J, Corper AL, Basler CF et al. Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science303(5665), 1866–1870 (2004).
  • Skehel JJ, Wiley DC. Influenza haemagglutinin. Vaccine20(Suppl. 2), S51–S54 (2002).
  • Mitnaul LJ, Matrosovich MN, Castrucci MR et al. Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza a virus. J. Virol.74(13), 6015–6020 (2000).
  • Tsuchiya E, Sugawara K, Hongo S et al. Effect of addition of new oligosaccharide chains to the globular head of influenza A/H2N2 virus haemagglutinin on the intracellular transport and biological activities of the molecule. J. Gen. Virol.83(Pt 5), 1137–1146 (2002).
  • Honda Y, Takahashi H, Kuroki Y, Akino T, Abe S. Decreased contents of surfactant proteins A and D in BAL fluids of healthy smokers. Chest109, 1006–1009 (1996).
  • Postle A, Mander A, Reid K et al. Deficient Hydrophilic surfactant proteins A and D with normal surfactant phospholipid molecular species in cystic fibrosis. Am. J. Respir. Cell Mol. Biol.20, 90–98 (1999).
  • Sims MW, Tal-Singer RM, Kierstein S et al. Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study. Respir. Res.9, 13 (2008).
  • White MR, Tecle T, Crouch EC, Hartshorn KL. Impact of neutrophils on antiviral activity of human bronchoalveolar lavage fluid. Am. J. Physiol. Lung Cell. Mol. Physiol.293(5), L1293–L1299 (2007).
  • Reading P, Allison J, Crouch E, Anders E. Increased susceptibility of diabetic mice to influenza virus infection: compromise of collectin-mediated host defense of the lung by glucose. J. Virol.72, 6884–6887 (1998).
  • Hartshorn KL, White MR, Tecle T et al. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D. Respir. Res.8, 9 (2007).
  • LahtI M, Lofgren J, Martilla T et al. Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection. Pediatr. Res.51(6), 696–699 (2002).
  • Floros J, Lin H, Garcia A et al. Surfactant protein marker alleles identify a subgroup of tuberculosis patients in a Mexican population. J. Infect. Dis.182, 1473–1478 (2000).
  • Koch A, Melbye M, Sorensen P et al. Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood. JAMA285, 1316–1321 (2001).
  • Wright JR. Immunoregulatory functions of surfactant proteins. Nat. Rev. Immunol.5(1), 58–68 (2005).
  • Hartshorn KL, White MR, Shepherd V et al. Mechanisms of anti-influenza activity of surfactant proteins A and D: comparison with serum collectins. Am. J. Physiol.273(6 Pt 1), L1156–L1166 (1997).
  • van Eijk M, White MR, Batenburg JJ et al. Interactions of influenza A virus with sialic acids present on porcine surfactant protein D. Am. J. Respir. Cell Mol. Biol.30(6), 871–879 (2004).
  • Baumgarth N, Herman OC, Jager GC et al. B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J. Exp. Med.192(2), 271–280 (2000).
  • Jayasekera JP, Moseman EA, Carroll MC. Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity. J. Virol.81(7), 3487–3494 (2007).
  • Watford W, Chio A, Wright J. Complement-mediated host defense in the lung. Am. J. Physiol.279, L790–L798 (2000).
  • Ezekowitz RA. Role of the mannose-binding lectin in innate immunity. J. Infect. Dis.187(Suppl. 2), S335–S339 (2003).
  • Anders EM, Hartley CA, Reading PC, Ezekowitz RAB. Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin. J. Gener. Virol.75, 615–622 (1994).
  • Kim AH, Dimitriou ID, Holland MC et al. Complement C5a receptor is essential for the optimal generation of antiviral CD8+ T cell responses. J. Immunol.173(4), 2524–2529 (2004).
  • Kopf M, Abel B, Gallimore A, Carroll M, Bachmann MF. Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection. Nat. Med.8(4), 373–378 (2002).
  • Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat. Rev.3, 710–720 (2003).
  • Salvatore M, Garcia-Sastre A, Ruchala P et al. α-defensin inhibits influenza virus replication by cell-mediated mechanism(s). J. Infect. Dis.196(6), 835–843 (2007).
  • Daly NL, Chen YK, Rosengren KJ et al. Retrocyclin-2: structural analysis of a potent anti-HIV t-defensin. Biochemistry46(35), 9920–9928 (2007).
  • Hartshorn KL, White MR, Tecle T, Holmskov U, Crouch EC. Innate defense against influenza A virus: activity of human neutrophil defensins and interactions of defensins with surfactant protein D. J. Immunol.176(11), 6962–6972 (2006).
  • Tecle T, White MR, Gantz D, Crouch EC, Hartshorn KL. Human neutrophil defensins increase neutrophil uptake of influenza A virus and bacteria and modify virus-induced respiratory burst responses. J. Immunol.178(12), 8046–8052 (2007).
  • Seth RB, Sun L, Chen ZJ. Antiviral innate immunity pathways. Cell Res.16(2), 141–147 (2006).
  • Diebold S, Kaisho T, Hemmi H, Akira S, Sousa CE. Innate antiviral responses by means of TLR7-mediated recognition of single stranded RNA. Science303, 1529–1531 (2004).
  • Wang JP, Liu P, Latz E et al. Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition. J. Immunol.177(10), 7114–7121 (2006).
  • Le Goffic R, Pothlichet J, Vitour D et al. Cutting edge: influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells. J. Immunol.178(6), 3368–3372 (2007).
  • Guillot L, Le Goffic R, Bloch S et al. Involvement of Toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J. Biol. Chem.280(7), 5571–5580 (2005).
  • Le Goffic R, Balloy V, Lagranderie M et al. Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog.2(6), e53 (2006).
  • Pichlmair A, Schulz O, Tan CP et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5´-phosphates. Science314(5801), 997–1001 (2006).
  • Loo YM, Fornek J, Crochet N et al. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J. Virol.82(1), 335–345 (2008).
  • Kato H, Takeuchi O, Sato S et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature441(7089), 101–105 (2006).
  • Sun Q, Sun L, Liu HH et al. The specific and essential role of MAVS in antiviral innate immune responses. Immunity24(5), 633–642 (2006).
  • Koyama S, Ishii KJ, Kumar H et al. Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination. J. Immunol.179(7), 4711–4720 (2007).
  • Lund JM, Alexopoulou L, Sato A et al. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc. Natl Acad. Sci. USA101(15), 5598–5603 (2004).
  • Wurzer WJ, Ehrhardt C, Pleschka S et al. NF-κB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation. J. Biol. Chem.279(30), 30931–30937 (2004).
  • Wurzer WJ, Planz O, Ehrhardt C et al. Caspase 3 activation is essential for efficient influenza virus propagation. EMBO J.22(11), 2717–2728 (2003).
  • Bernasconi D, Amici C, La Frazia S, Ianaro A, Santoro MG. The IκB kinase is a key factor in triggering influenza A virus-induced inflammatory cytokine production in airway epithelial cells. J. Biol. Chem.280(25), 24127–24134 (2005).
  • Wei L, Sandbulte MR, Thomas PG et al. NFκB negatively regulates interferon-induced gene expression and anti-influenza activity. J. Biol. Chem.281(17), 11678–11684 (2006).
  • Pothlichet J, Chignard M, Si-Tahar M. Cutting edge: innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway. J. Immunol.180(4), 2034–2038 (2008).
  • Marjuki H, Alam MI, Ehrhardt C et al. Membrane accumulation of influenza A virus hemagglutinin triggers nuclear export of the viral genome via protein kinase Ca-mediated activation of ERK signaling. J. Biol. Chem.281(24), 16707–16715 (2006).
  • Hartshorn KL, Wright J, Collamer M, White MR, Tauber AI. Human neutrophil stimulation by influenza virus: relationship of cytoplasmic pH changes to cell activation. Am. J. Physiol.258, C1070–C1076 (1990).
  • Hartshorn KL, Collamer M, White MR, Schwartz JH, Tauber AI. Characterization of influenza A virus activation of the human neutrophil. Blood75(1), 218–226 (1990).
  • Lee DC, Cheung CY, Law AH et al. p38 mitogen-activated protein kinase-dependent hyperinduction of tumor necrosis factor a expression in response to avian influenza virus H5N1. J. Virol.79(16), 10147–10154 (2005).
  • Garcia-Sastre A. Antiviral response in pandemic influenza viruses. Emerg. Infect. Dis.12(1), 44–47 (2006).
  • Garcia-Sastre A, Durbin R, Zheng H et al. The role of interferon in influenza virus tissue tropism. J. Virol.72, 8550–8558 (1998).
  • Price GE, Gaszewska-Mastarlarz A, Moskophidis D. The role of α/β and g interferons in development of immunity to influenza A virus in mice. J. Virol.74(9), 3996–4003 (2000).
  • Wang X, Ming L, Zheng H et al. Influenza A virus NS1 protein prevents activation of NFκB and induction of α/β interferon. J. Virol.74, 11566–11573 (2000).
  • Geiss G, Salvatore M, Tumpey T et al. Cellular transcription profiling in influenza A virus-infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza. Proc. Natl Acad. Sci. USA99, 10736–10741 (2002).
  • Jewell NA, Vaghefi N, Mertz SE et al. Differential type I interferon induction by respiratory syncytial virus and influenza A virus in vivo. J. Virol.81(18), 9790–9800 (2007).
  • Hayden F, Fritz R, Lobo M et al. Local and systemic cytokine response during experimental human influenza A virus infection. J. Clin. Invest.101, 643–649 (1998).
  • Lee N, Wong CK, Chan PK et al. Hypercytokinemia and hyperactivation of phospho-p38 mitogen-activated protein kinase in severe human influenza A virus infection. Clin. Infect. Dis.45(6), 723–731 (2007).
  • Denton AE, Doherty PC, Turner SJ, La Gruta NL. IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cells. Eur. J. Immunol.37(2), 368–375 (2007).
  • Szretter KJ, Gangappa S, Lu X et al. Role of host cytokine responses in the pathogenesis of avian H5N1 influenza viruses in mice. J. Virol.81(6), 2736–2744 (2007).
  • Schmitz N, Kurrer M, Bachmann MF, Kopf M. Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection. J. Virol.79(10), 6441–6448 (2005).
  • Van Der Sluijs KF, Van Elden LJ, Nijhuis M et al. IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection. J. Immunol.172(12), 7603–7609 (2004).
  • Zeng H, Goldsmith C, Thawatsupha P et al. Highly pathogenic avian influenza H5N1 viruses elicit an attenuated type I interferon response in polarized human bronchial epithelial cells. J. Virol.81(22), 12439–12449 (2007).
  • Chan MC, Cheung CY, Chui WH et al. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir. Res.6, 135 (2005).
  • Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk H. Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proc. Natl Acad. Sci. USA101(13), 4620–4624 (2004).
  • van Riel D, Munster VJ, de Wit E et al. H5N1 Virus attachment to lower respiratory tract. Science312(5772), 399 (2006).
  • Kido H, Yokogoshi Y, Sakai K, Tashiro M, Kishino Y. Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial clara cells. J. Biol. Chem.267, 13573–13579 (1992).
  • Hashimoto Y, Moki T, Takizawa T, Shiratsuchi A, Nakanishi Y. Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. J. Immunol.178(4), 2448–2457 (2007).
  • Arndt U, Wennemuth G, Barth P et al. Release of macrophage migration inhibitory factor and CXCL8/interleukin-8 from lung epithelial cells rendered necrotic by influenza A virus infection. J. Virol.76(18), 9298–9306 (2002).
  • Meyerholz DK, Kawashima K, Gallup JM, Grubor B, Ackermann MR. Expression of select immune genes (surfactant proteins A and D, sheep β defensin 1, and Toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb. Dev. Comp. Immunol.30(11), 1060–1069 (2006).
  • Grayson MH, Holtzman MJ. Emerging role of dendritic cells in respiratory viral infection. J. Mol. Med.85(10), 1057–1068 (2007).
  • Lopez CB, Moltedo B, Alexopoulou L et al. TLR-independent induction of dendritic cell maturation and adaptive immunity by negative-strand RNA viruses. J. Immunol.173(11), 6882–6889 (2004).
  • Colina R, Costa-Mattioli M, Dowling RJ et al. Translational control of the innate immune response through IRF-7. Nature452(7185), 323–328 (2008).
  • Dai J, Megjugorac NJ, Amrute SB, Fitzgerald-Bocarsly P. Regulation of IFN regulatory factor-7 and IFN-α production by enveloped virus and lipopolysaccharide in human plasmacytoid dendritic cells. J. Immunol.173(3), 1535–1548 (2004).
  • Piqueras B, Connolly J, Freitas H, Palucka AK, Banchereau J. Upon viral exposure, myeloid and plasmacytoid dendritic cells produce 3 waves of distinct chemokines to recruit immune effectors. Blood107(7), 2613–2618 (2006).
  • Draghi M, Pashine A, Sanjanwala B et al. NKp46 and NKG2D recognition of infected dendritic cells is necessary for NK cell activation in the human response to influenza infection. J. Immunol.178(5), 2688–2698 (2007).
  • Thitithanyanont A, Engering A, Ekchariyawat P et al. High susceptibility of human dendritic cells to avian influenza H5N1 virus infection and protection by IFN-α and TLR ligands. J. Immunol.179(8), 5220–5227 (2007).
  • Fernandez-Sesma A, Marukian S, Ebersole BJ et al. Influenza virus evades innate and adaptive immunity via the NS1 protein. J. Virol.80(13), 6295–6304 (2006).
  • Gazit R, Gruda R, Elboim M et al. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nat. Immunol.7(5), 517–523 (2006).
  • Mandelboim O, Lieberman N, Lev M et al. Recognition of haemagglutinins of virus-infected cells by NKp46 activates lysis by NK cells. Nature409, 1055–1060 (2001).
  • Ho JW, Hershkovitz O, Peiris M et al. H5-type influenza hemagglutinin is functionally recognized by the natural killer activating receptor, NKp44. J. Virol.82(4), 2028–2032 (2007).
  • Owen RE, Yamada E, Thompson CI et al. Alterations in receptor binding properties of recent human influenza H3N2 viruses are associated with reduced natural killer cell lysis of infected cells. J. Virol.81(20), 11170–11178 (2007).
  • Watanabe Y, Hashimoto Y, Shiratsuchi A, Takizawa T, Nakanishi Y. Augmentation of fatality of influenza in mice by inhibition of phagocytosis. Biochem. Biophys. Res. Commun.337(3), 881–886 (2005).
  • van der Sluijs KF, van Elden L, Nijhuis M et al. Toll-like receptor 4 is not involved in host defense against respiratory tract infection with Sendai virus. Immunol. Lett.89(2–3), 201–206 (2003).
  • Cassidy L, Lyles D, Abramson J. Synthesis of viral proteins in polymorphonuclear leukocytes infected with influenza A virus. J. Clin. Microbiol.26, 1267–1270 (1988).
  • Sweet C, Bird RA, Howie AJ et al. Further studies of the reasons for the lack of alveolar infection during influenza in ferrets. Br. J. Exp. Pathol.66(2), 217–231 (1985).
  • Kim HM, Lee YW, Lee KJ et al. Alveolar macrophages are indispensable for controlling influenza viruses in lungs of pigs. J. Virol.82(9), 4265–4274 (2008).
  • Fujisawa H, Tsuru S, Taniguchi M, Zinnaka Y, Nomoto K. Protective Mechanisms against pulmonary infection with influenza virus. I. Relative contribution of polymorphonuclear leukocytes and of alveolar mactrophages to protection during the early phase of intranasal infection. J. Gen. Virol.68, 425–432 (1987).
  • Tumpey TM, Garcia-Sastre A, Taubenberger JK et al. Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J. Virol.79(23), 14933–14944 (2005).
  • Conenello GM, Zamarin D, Perrone LA, Tumpey T, Palese P. A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog.3(10), 1414–1421 (2007).
  • Zamarin D, Garcia-Sastre A, Xiao X, Wang R, Palese P. Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLoS Pathog.1(1), e4 (2005).
  • Lin KL, Suzuki Y, Nakano H, Ramsburg E, Gunn MD. CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J. Immunol.180(4), 2562–2572 (2008).
  • Baskin CR, Bielefeldt-Ohmann H, Garcia-Sastre A et al. Functional genomic and serological analysis of the protective immune response resulting from vaccination of macaques with an NS1-truncated influenza virus. J. Virol.81(21), 11817–11827 (2007).
  • Baas T, Baskin CR, Diamond DL et al. Integrated molecular signature of disease: analysis of influenza virus-infected macaques through functional genomics and proteomics. J. Virol.80(21), 10813–10828 (2006).
  • Baskin CR, Garcia-Sastre A, Tumpey TM et al. Integration of clinical data, pathology, and cDNA microarrays in influenza virus-infected pigtailed macaques (Macaca nemestrina). J. Virol.78(19), 10420–10432 (2004).
  • Smith H, Sweet C. Lessons for human influenza from pathogenicity studies with ferrets. Rev. Infect. Dis.10, 56–75 (1988).
  • Wareing MD, Shea AL, Inglis CA, Dias PB, Sarawar SR. CXCR2 is required for neutrophil recruitment to the lung during influenza virus infection, but is not essential for viral clearance. Viral Immunol.20(3), 369–378 (2007).
  • Snelgrove RJ, Edwards L, Rae AJ, Hussell T. An absence of reactive oxygen species improves the resolution of lung influenza infection. Eur. J. Immunol.36(6), 1364–1373 (2006).
  • Sakai S, Kawamata H, Mantani N et al. Therapeutic effect of anti-macrophage inflammatory protein 2 antibody on influenza virus-induced pneumonia in mice. J. Virol.74(5), 2472–2476 (2000).
  • Tsuru S, Fujisawa H, Taniguchi M, Zinnaka Y, Nomoto K. Mechanism of protection during the early phase of a generalized viral infection II. Contribution of polymorphonuclear leukocytes to protection against intravenous infection with influenza virus. J. Gen. Virol.68, 419–424 (1987).
  • Kobasa D, Jones SM, Shinya K et al. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature445(7125), 319–323 (2007).
  • Kobasa D, Takada A, Shinya K et al. Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature431(7009), 703–707 (2004).
  • Hartshorn KL, Daigneault DE, White MR, Tauber AI. Anomalous features of human neutrophil activation by influenza A virus are shared by related viruses and sialic acid-binding lectins. J. Leuk. Biol.51, 230–236 (1992).
  • Dawson TC, Beck MA, Kuziel WA, Henderson F, Maeda N. Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus. Am. J. Pathol.156(6), 1951–1959 (2000).
  • Tumpey T, Garcia-Sastre A, Taubenberger J, Palese P, Swayne D. Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus. Proc. Natl Acad. Sci. USA101(9), 3166–3171 (2004).
  • Abdel-Ghafar AN, Chotpitayasunondh T, Gao Z et al. Update on avian influenza A (H5N1) virus infection in humans. N. Engl. J. Med.358(3), 261–273 (2008).
  • de Jong MD, Simmons CP, ThanhTT et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat. Med.12(10), 1203–1207 (2006).
  • Jayasekera JP, Vinuesa CG, Karupiah G, King NJ. Enhanced antiviral antibody secretion and attenuated immunopathology during influenza virus infection in nitric oxide synthase-2-deficient mice. J. Gen. Virol.87(Pt 11), 3361–3371 (2006).
  • Karupiah G, Chen JH, Mahalingam S, Nathan CF, MacMicking JD. Rapid interferon γ-dependent clearance of influenza A virus and protection from consolidating pneumonitis in nitric oxide synthase 2-deficient mice. J. Exp. Med.188(8), 1541–1546 (1998).
  • Zaki MH, Akuta T, Akaike T. Nitric oxide-induced nitrative stress involved in microbial pathogenesis. J. Pharmacol. Sci.98(2), 117–129 (2005).
  • Akaike T, Okamoto S, Sawa T et al. 8-nitroguanosine formation in viral pneumonia and its implication for pathogenesis. Proc. Natl Acad. Sci. USA100(2), 685–690 (2003).
  • Akaike T, Noguchi Y, Ijiri S et al. Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. Proc. Natl Acad. Sci. USA93, 2448–2453 (1996).
  • Yoshitake J, Akaike T, Akuta T et al. Nitric oxide as an endogenous mutagen for Sendai virus without antiviral activity. J. Virol.78(16), 8709–8719 (2004).
  • Akaike T. Role of free radicals in viral pathogenesis and mutation. Rev. Med. Virol.11(2), 87–101 (2001).
  • Akaike T, Ando M, Oda T et al. Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice. J. Clin. Invest.85(3), 739–745 (1990).
  • Oda T, Akaike T, Hamamoto T et al. Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD. Science244(4907), 974–976 (1989).
  • Imai Y, Kuba K, Neely GG et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell133(2), 235–249 (2008).
  • Xu L, Yoon H, Zhao MQ et al. Cutting edge: pulmonary immunopathology mediated by antigen-specific expression of TNF-α by antiviral CD8+ T cells. J. Immunol.173(2), 721–725 (2004).
  • Speshock JL, Doyon-Reale N, Rabah R, Neely MN, Roberts PC. Filamentous influenza A virus infection predisposes mice to fatal septicemia following superinfection with Streptococcus pneumoniae serotype 3. Infect. Immun.75(6), 3102–3111 (2007).
  • McNamee LA, Harmsen AG. Both influenza-induced neutrophil dysfunction and neutrophil-independent mechanisms contribute to increased susceptibility to a secondary Streptococcus pneumoniae infection. Infect. Immun.74(12), 6707–6721 (2006).
  • McCullers JA, Bartmess KC. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J. Infect. Dis.187, 1000–1009 (2003).
  • Abramson JS, Giebink GS, Quie PG. Influenza A virus-induced polymorphonuclear leukocyte dysfunction in the pathogenesis of experimental pneumococcal otitis media. Infect. Immun.36, 289–296 (1982).
  • Hartshorn KL, Liou LS, White MR, Kazhdan MM, Tauber JL. Neutrophil deactivation by influenza A virus: role of hemagglutinin binding to specific sialic acid-bearing cellular proteins. J. Immunol.154, 3952–3960 (1995).
  • Hartshorn K, Reid K, White M et al. Neutrophil deactivation by influenza A viruses: mechanisms of protection after viral opsonization with collectins and hemagglutination-inhibiting antibodies. Blood87, 3450–3461 (1996).
  • LeVine A, Whitsett J, Hartshorn K, Korfhagen T. Surfactant protein D enhances clearance of influenza A virus from the lung in vivo.J. Immunol.167, 5868–5873 (2001).
  • Colamussi ML, White MR, Crouch E, Hartshorn KL. Influenza A virus accelerates neutrophil apoptosis and markedly potentiates apoptotic effects of bacteria. Blood93(7), 2395–2403 (1999).
  • Didierlaurent A, Goulding J, Patel S et al. Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection. J. Exp. Med.205(2), 323–329 (2008).
  • McAuley JL, Hornung F, Boyd KL et al. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe2(4), 240–249 (2007).
  • Marsland BJ, Scanga CB, Kopf M, Le Gros G. Allergic airway inflammation is exacerbated during acute influenza infection and correlates with increased allergen presentation and recruitment of allergen-specific T-helper type 2 cells. Clin. Exp. Allergy34(8), 1299–1306 (2004).
  • Izurieta HS, Thompson WW, Kramarz P et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N. Engl. J. Med.342(4), 232–239 (2000).
  • Dahl M, Dabbagh K, Liggitt D, Kim S, Lewis D. Viral-induced T helper 1 responses enhance allergic disease by effects on lung dendritic cells. Nat. Immunol.5, 337–343 (2004).
  • Tsitoura D, Kim S, Dabbagh K et al. Respiratory infection with influenza A virus interferes with the induction of tolerance to aeroallergens. J. Immunol.165, 3484–3491 (2000).
  • Strong P, Reid K, Clark H. Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus. Clin. Exp. Immunol.130, 19–24 (2002).
  • Atochina EN, Beers MF, Tomer Y et al. Attenuated allergic airway hyperresponsiveness in C57BL/6 mice is associated with enhanced surfactant protein (SP)-D production following allergic sensitization. Respir. Res.4(15), 1–12 (2003).
  • Le Bon A, Durand V, Kamphuis E et al. Direct stimulation of T cells by type I IFN enhances the CD8+ T cell response during cross-priming. J. Immunol.176(8), 4682–4689 (2006).
  • Bracci L, Canini I, Venditti M et al. Type I IFN as a vaccine adjuvant for both systemic and mucosal vaccination against influenza virus. Vaccine24(Suppl. 2), S2–56–57 (2006).
  • Coro ES, Chang WL, Baumgarth N. Type I IFN receptor signals directly stimulate local B cells early following influenza virus infection. J. Immunol.176(7), 4343–4351 (2006).
  • Takeshita F, Tanaka T, Matsuda T et al. Toll-like receptor adaptor molecules enhance DNA-raised adaptive immune responses against influenza and tumors through activation of innate immunity. J. Virol.80(13), 6218–6224 (2006).
  • Fillatreau S, Manz RA. Tolls for B cells. Eur. J. Immunol.36(4), 798–801 (2006).
  • Tacchini-Cottier F, Zweifel C, Belkaid Y et al. An immunomodulatory function for neutrophils during the induction of a CD4+ Th2 response in BALB/c mice infected with Leishmania major.J. Immunol.165(5), 2628–2636 (2000).
  • Tezuka H, Abe Y, Iwata M et al. Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. Nature448(7156), 929–933 (2007).
  • Zhou J, Matsuoka M, Cantor H, Homer R, Enelow RI. Cutting edge: engagement of NKG2A on CD8+ effector T cells limits immunopathology in influenza pneumonia. J. Immunol.180(1), 25–29 (2008).
  • Knudsen L, Ochs M, Mackay R et al. Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice. Respir. Res.8(1), 70 (2007).
  • Palaniyar N, Clark H, Nadesalingam J et al. Innate immune collectin surfactant protein D enhances the clearance of DNA by macrophages and minimizes anti-DNA antibody generation. J. Immunol.174(11), 7352–7358 (2005).
  • Liu CF, Chen YL, Shieh CC et al. Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice. Clin. Exp. Allergy35(4), 515–521 (2005).
  • Clark H, Palaniyar N, Strong P et al. Surfactant protein D reduces alveolar macrophage apoptosis in vivo.J. Immunol.169, 2892–2899 (2002).
  • Hickling T, Bright H, Wing K et al. A recombinant trimeric surfactant protein D carbohydrate recognition domain inhibits respiratory synctitial virus infection in vitro and in vivo.Eur. J. Immunol.29, 3478–3484 (1999).
  • Crouch E, Tu Y, Briner D et al. Ligand specificity of human surfactant protein D: expression of a mutant trimeric collectin that shows enhanced interactions with influenza A virus. J. Biol. Chem.280(17), 17046–17056 (2005).
  • Tecle T, White MR, Sorensen GL et al. Critical role for crosslinking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus. Biochem. J. (2008) (In Press).
  • Tacken PJ, Hartshorn KL, White MR et al. Effective targeting of pathogens to neutrophils via chimeric surfactant protein D/anti-CD89 protein. J. Immunol.172(8), 4934–4940 (2004).
  • Zhang H, Porro G, Orzech N et al. Neutrophil defensins mediate acute inflammatory response and lung dysfunction in dose-related fashion. Am. J. Physiol. Lung Cell. Mol. Physiol.280(5), L947–L954 (2001).
  • Wu CC, Hayashi T, Takabayashi K et al. Immunotherapeutic activity of a conjugate of a Toll-like receptor 7 ligand. Proc. Natl Acad. Sci. USA104(10), 3990–3995 (2007).
  • Hammerbeck DM, Burleson GR, Schuller CJ et al. Administration of a dual Toll-like receptor 7 and Toll-like receptor 8 agonist protects against influenza in rats. Antiviral Res.73(1), 1–11 (2007).
  • Mazur I, Wurzer WJ, Ehrhardt C et al. Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-κB-inhibiting activity. Cell. Microbiol.9(7), 1683–1694 (2007).
  • Welliver TP, Garofalo RP, Hosakote Y et al. Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. J. Infect. Dis.195(8), 1126–1136 (2007).
  • Zheng B, Zhang Y, He H et al. Rectification of age-associated deficiency in cytotoxic T cell response to influenza A virus by immunization with immune complexes. J. Immunol.179(9), 6153–6159 (2007).
  • Deng Y, Jing Y, Campbell AE, Gravenstein S. Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. J. Immunol.172(6), 3437–3446 (2004).
  • Boehmer ED, Goral J, Faunce DE, Kovacs EJ. Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression. J. Leukoc. Biol.75(2), 342–349 (2004).
  • Seo S, Hoffman E, Webster R. Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat. Med.8, 950–954 (2002).
  • Salomon R, Hoffmann E, Webster RG. Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc. Natl Acad. Sci. USA104(30), 12479–12481 (2007).

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