1887

Abstract

gene-deficient (NOS2) mice are less susceptible than wild-type (NOS2) mice to infection with . Virus titres in the lungs of influenza-infected NOS2 mice are significantly lower than those in NOS2 mice, with enhanced viral clearance in NOS2 mice dependent on gamma interferon (IFN-). The current study was undertaken to ascertain the role of specific components of the immune response in promoting virus clearance in influenza-infected NOS2 mice. Levels of T cell- and natural killer cell-mediated cytotoxicity in the lungs of virus-infected mice were not significantly different between NOS2 and NOS2 mice. However, virus-infected NOS2 mice produced higher levels of virus-specific IgG2a antibody. Furthermore, more viable B cells and plasmablasts, along with greater levels of IFN-, were found in NOS2 splenocyte cultures stimulated with B-cell mitogens. In addition to the early reduction in virus titres, clinical symptoms and proinflammatory cytokine production were attenuated in NOS2 mice. Thus, NOS2 B cells are capable of responding rapidly to influenza virus infection by proliferating and preferentially producing antibody of the IgG2a subtype. The relationship between viral load and the development of immunopathology is discussed.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82131-0
2006-11-01
2019-11-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/11/3361.html?itemId=/content/journal/jgv/10.1099/vir.0.82131-0&mimeType=html&fmt=ahah

References

  1. Adler, H., Beland, J. L., Del-Pan, N. C., Kobzik, L., Brewer, J. P., Martin, T. R. & Rimm, I. J. ( 1997; ). Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2). J Exp Med 185, 1533–1540.[CrossRef]
    [Google Scholar]
  2. Akaike, T., Noguchi, Y., Ijiri, S., Setoguchi, K., Suga, M., Zheng, Y. M., Dietzschold, B. & Maeda, H. ( 1996; ). Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. Proc Natl Acad Sci U S A 93, 2448–2453.[CrossRef]
    [Google Scholar]
  3. Akaike, T., Okamoto, S., Sawa, T., Yoshitake, J., Tamura, F., Ichimori, K., Miyazaki, K., Sasamoto, K. & Maeda, H. ( 2003; ). 8-Nitroguanosine formation in viral pneumonia and its implication for pathogenesis. Proc Natl Acad Sci U S A 100, 685–690.[CrossRef]
    [Google Scholar]
  4. Bachmann, M. F. & Zinkernagel, R. M. ( 1996; ). The influence of virus structure on antibody responses and virus serotype formation. Immunol Today 17, 553–558.[CrossRef]
    [Google Scholar]
  5. Balázs, M., Martin, F., Zhou, T. & Kearney, J. F. ( 2002; ). Blood dendritic cells interact with splenic marginal zone B cells to initiate T-independent immune responses. Immunity 17, 341–352.[CrossRef]
    [Google Scholar]
  6. Batten, M., Groom, J., Cachero, T. G., Qian, F., Schneider, P., Tschopp, J., Browning, J. L. & Mackay, F. ( 2000; ). BAFF mediates survival of peripheral immature B lymphocytes. J Exp Med 192, 1453–1466.[CrossRef]
    [Google Scholar]
  7. Baumgarth, N. & Kelso, A. ( 1996; ). In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue. J Virol 70, 4411–4418.
    [Google Scholar]
  8. Beebe, D. P., Schreiber, R. D. & Cooper, N. R. ( 1983; ). Neutralization of influenza virus by normal human sera: mechanisms involving antibody and complement. J Immunol 130, 1317–1322.
    [Google Scholar]
  9. Bender, B. S., Croghan, T., Zhang, L. & Small, P. A., Jr ( 1992; ). Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med 175, 1143–1145.[CrossRef]
    [Google Scholar]
  10. Cerwenka, A., Morgan, T. M., Harmsen, A. G. & Dutton, R. W. ( 1999; ). Migration kinetics and final destination of type 1 and type 2 CD8 effector cells predict protection against pulmonary virus infection. J Exp Med 189, 423–434.[CrossRef]
    [Google Scholar]
  11. Conn, C. A., McClellan, J. L., Maassab, H. F., Smitka, C. W., Majde, J. A. & Kluger, M. J. ( 1995; ). Cytokines and the acute phase response to influenza virus in mice. Am J Physiol 268, R78–R84.
    [Google Scholar]
  12. Coutelier, J.-P., van der Logt, J. T. M., Heessen, F. W. A., Warnier, G. & Van Snick, J. ( 1987; ). IgG2a restriction of murine antibodies elicited by viral infections. J Exp Med 165, 64–69.[CrossRef]
    [Google Scholar]
  13. Eichelberger, M., Allan, W., Zijlstra, M., Jaenisch, R. & Doherty, P. C. ( 1991; ). Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. J Exp Med 174, 875–880.[CrossRef]
    [Google Scholar]
  14. Feng, J. Q., Mozdzanowska, K. & Gerhard, W. ( 2002; ). Complement component C1q enhances the biological activity of influenza virus hemagglutinin-specific antibodies depending on their fine antigen specificity and heavy-chain isotype. J Virol 76, 1369–1378.[CrossRef]
    [Google Scholar]
  15. Fritz, R. S., Hayden, F. G., Calfee, D. P., Cass, L. M. r., Peng, A. W., Alvord, W. G., Strober, W. & Straus, S. E. ( 1999; ). Nasal cytokine and chemokine responses in experimental influenza A virus infection: results of a placebo-controlled trial of intravenous zanamivir treatment. J Infect Dis 180, 586–593.[CrossRef]
    [Google Scholar]
  16. Garthwaite, J. ( 1991; ). Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14, 60–67.[CrossRef]
    [Google Scholar]
  17. Graham, M. B., Dalton, D. K., Giltinan, D., Braciale, V. L., Stewart, T. A. & Braciale, T. J. ( 1993; ). Response to influenza infection in mice with a targeted disruption in the interferon γ gene. J Exp Med 178, 1725–1732.[CrossRef]
    [Google Scholar]
  18. Hasbold, J., Hong, J. S., Kehry, M. R. & Hodgkin, P. D. ( 1999; ). Integrating signals from IFN-γ and IL-4 by B cells: positive and negative effects on CD40 ligand-induced proliferation, survival, and division-linked isotype switching to IgG1, IgE, and IgG2a. J Immunol 163, 4175–4181.
    [Google Scholar]
  19. Hayden, F. G., Fritz, R., Lobo, M. C., Alvord, W., Strober, W. & Straus, S. E. ( 1998; ). Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest 101, 643–649.[CrossRef]
    [Google Scholar]
  20. Iwasaki, T. & Nozima, T. ( 1977; ). Defense mechanisms against primary influenza virus infection in mice. I. The roles of interferon and neutralizing antibodies and thymus dependence of interferon and antibody production. J Immunol 118, 256–263.
    [Google Scholar]
  21. Jackson, D. C., Tang, X.-L., Brown, L. E., Murray, J. M., White, D. O. & Tregear, G. W. ( 1986; ). Antigenic determinants of influenza virus hemagglutinin. XII. The epitopes of a synthetic peptide representing the C-terminus of HA1. Virology 155, 625–632.[CrossRef]
    [Google Scholar]
  22. James, S. L., Cheever, A. W., Caspar, P. & Wynn, T. A. ( 1998; ). Inducible nitric oxide synthase-deficient mice develop enhanced type 1 cytokine-associated cellular and humoral immune responses after vaccination with attenuated Schistosoma mansoni cercariae but display partially reduced resistance. Infect Immun 66, 3510–3518.
    [Google Scholar]
  23. Karupiah, G., Xie, Q. W., Buller, R. M., Nathan, C., Duarte, C. & MacMicking, J. D. ( 1993; ). Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science 261, 1445–1448.[CrossRef]
    [Google Scholar]
  24. Karupiah, G., Chen, J.-H., Mahalingam, S., Nathan, C. F. & MacMicking, J. D. ( 1998a; ). 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, 1541–1546.[CrossRef]
    [Google Scholar]
  25. Karupiah, G., Chen, J.-H., Nathan, C. F., Mahalingam, S. & MacMicking, J. D. ( 1998b; ). Identification of nitric oxide synthase 2 as an innate resistance locus against ectromelia virus infection. J Virol 72, 7703–7706.
    [Google Scholar]
  26. Kipps, T. J., Parham, P., Punt, J. & Herzenberg, L. A. ( 1985; ). Importance of immunoglobulin isotype in human antibody-dependent, cell-mediated cytotoxicity directed by murine monoclonal antibodies. J Exp Med 161, 1–17.[CrossRef]
    [Google Scholar]
  27. Kobasa, D., Takada, A., Shinya, K. & 16 other authors ( 2004; ). Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature 431, 703–707.[CrossRef]
    [Google Scholar]
  28. Kozak, W., Poli, V., Soszynski, D., Conn, C. A., Leon, L. R. & Kluger, M. J. ( 1997; ). Sickness behavior in mice deficient in interleukin-6 during turpentine abscess and influenza pneumonitis. Am J Physiol 272, R621–R630.
    [Google Scholar]
  29. Lyons, A. B. & Parish, C. R. ( 1994; ). Determination of lymphocyte division by flow cytometry. J Immunol Methods 171, 131–137.[CrossRef]
    [Google Scholar]
  30. MacMicking, J. D., North, R. J., LaCourse, R., Mudgett, J. S., Shah, S. K. & Nathan, C. F. ( 1997; ). Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc Natl Acad Sci U S A 94, 5243–5248.[CrossRef]
    [Google Scholar]
  31. Mellion, B. T., Ignarro, L. J., Ohlstein, E. H., Pontecorvo, E. G., Hyman, A. L. & Kadowitz, P. J. ( 1981; ). Evidence for the inhibitory role of guanosine 3′, 5′-monophosphate in ADP-induced human platelet aggregation in the presence of nitric oxide and related vasodilators. Blood 57, 946–955.
    [Google Scholar]
  32. Michael, A., Hackett, J. J., Bennett, M., Kumar, V. & Yuan, D. ( 1989; ). Regulation of B lymphocytes by natural killer cells. Role of IFN-gamma. J Immunol 142, 1095–1101.
    [Google Scholar]
  33. Moore, P. A., Belvedere, O., Orr, A. & 19 other authors ( 1999; ). BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science 285, 260–263.[CrossRef]
    [Google Scholar]
  34. Mozdzanowska, K., Furchner, M., Maiese, K. & Gerhard, W. ( 1997; ). CD4+ T cells are ineffective in clearing a pulmonary infection with influenza type A virus in the absence of B cells. Virology 239, 217–225.[CrossRef]
    [Google Scholar]
  35. Nardelli, B., Belvedere, O., Roschke, V. & 8 other authors ( 2001; ). Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood 97, 198–204.[CrossRef]
    [Google Scholar]
  36. Neuberger, M. S. & Rajewsky, K. ( 1981; ). Activation of mouse complement by monoclonal mouse antibodies. Eur J Immunol 11, 1012–1016.[CrossRef]
    [Google Scholar]
  37. Noda, S., Tanaka, K., Sawamura, S. & 7 other authors ( 2001; ). Role of nitric oxide synthase type 2 in acute infection with murine cytomegalovirus. J Immunol 166, 3533–3541.[CrossRef]
    [Google Scholar]
  38. Palladino, G., Mozdzanowska, K., Washko, G. & Gerhard, W. ( 1995; ). Virus-neutralizing antibodies of immunoglobulin G (IgG) but not of IgM or IgA isotypes can cure influenza virus pneumonia in SCID mice. J Virol 69, 2075–2081.
    [Google Scholar]
  39. Palmer, R. M., Ferrige, A. G. & Moncada, S. ( 1987; ). Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327, 524–526.[CrossRef]
    [Google Scholar]
  40. Peper, R. L. & Van Campen, H. ( 1995; ). Tumor necrosis factor as a mediator of inflammation in influenza A viral pneumonia. Microb Pathog 19, 175–183.[CrossRef]
    [Google Scholar]
  41. Sarawar, S. R., Sangster, M., Coffman, R. L. & Doherty, P. C. ( 1994; ). Administration of anti-IFN-gamma antibody to beta 2-microglobulin-deficient mice delays influenza virus clearance but does not switch the response to a T helper cell 2 phenotype. J Immunol 153, 1246–1253.
    [Google Scholar]
  42. Sato, K., Suga, M., Akaike, T., Fujii, S., Muranaka, H., Doi, T., Maeda, H. & Ando, M. ( 1998; ). Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice. Am J Respir Crit Care Med 157, 853–857.[CrossRef]
    [Google Scholar]
  43. Saura, M., Zaragoza, C., McMillan, A., Quick, R. A., Hohenadl, C., Lowenstein, J. M. & Lowenstein, C. J. ( 1999; ). An antiviral mechanism of nitric oxide: inhibition of a viral protease. Immunity 10, 21–28.[CrossRef]
    [Google Scholar]
  44. Schiltknecht, E. & Ada, G. L. ( 1985; ). In vivo effects of cyclosporine on influenza A virus-infected mice. Cell Immunol 91, 227–239.[CrossRef]
    [Google Scholar]
  45. Shtrichman, R. & Samuel, C. E. ( 2001; ). The role of gamma interferon in antimicrobial immunity. Curr Opin Microbiol 4, 251–259.[CrossRef]
    [Google Scholar]
  46. Snapper, C. M., Yamaguchi, H., Moorman, M. A. & Mond, J. J. ( 1994; ). An in vitro model for T cell-independent induction of humoral immunity. A requirement for NK cells. J Immunol 152, 4884–4892.
    [Google Scholar]
  47. Stein-Streilein, J. & Guffee, J. ( 1986; ). In vivo treatment of mice and hamsters with antibodies to asialo GM1 increases morbidity and mortality to pulmonary influenza infection. J Immunol 136, 1435–1441.
    [Google Scholar]
  48. Sullivan, J. L., Mayner, R. E., Barry, D. W. & Ennis, F. A. ( 1976; ). Influenza virus infection in nude mice. J Infect Dis 133, 91–94.[CrossRef]
    [Google Scholar]
  49. Swiergiel, A. H., Smagin, G. N., Johnson, L. J. & Dunn, A. J. ( 1997; ). The role of cytokines in the behavioral responses to endotoxin and influenza virus infection in mice: effects of acute and chronic administration of the interleukin-1-receptor antagonist (IL-1ra). Brain Res 776, 96–104.[CrossRef]
    [Google Scholar]
  50. Szomolanyi-Tsuda, E. & Welsh, R. M. ( 1998; ). T-cell-independent antiviral antibody responses. Curr Opin Immunol 10, 431–435.[CrossRef]
    [Google Scholar]
  51. Takagi, K., Ae, S. & Suketa, Y. ( 1992; ). Effect of nitrite on cell growth and antibody production in mouse splenic B cells stimulated with lipopolysaccharide and B cell hybridomas. Chem Pharm Bull (Tokyo) 40, 419–422.[CrossRef]
    [Google Scholar]
  52. Takagi, K., Nukaya, I., Yasukawa, K. & Suketa, Y. ( 1994; ). Inhibitory mechanisms of antibody production by nitrogen oxides released from activated macrophages during the immune response: relationship to energy consumption. Immunol Cell Biol 72, 241–248.[CrossRef]
    [Google Scholar]
  53. Taylor-Robinson, A. W. ( 1997; ). Counter-regulation of T helper 1 cell proliferation by nitric oxide and interleukin-2. Biochem Biophys Res Commun 233, 14–19.[CrossRef]
    [Google Scholar]
  54. Topham, D. J., Tripp, R. A. & Doherty, P. C. ( 1997; ). CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J Immunol 159, 5197–5200.
    [Google Scholar]
  55. Unkeless, J. C. & Eisen, H. N. ( 1975; ). Binding of monomeric immunoglobulins to Fc receptors of mouse macrophages. J Exp Med 142, 1520–1533.[CrossRef]
    [Google Scholar]
  56. Wall, D. A., Hamberg, S. D., Reynolds, D. S., Burakoff, S. J., Abbas, A. K. & Ferrara, J. L. ( 1988; ). Immunodeficiency in graft-versus-host disease. I. Mechanism of immune suppression. J Immunol 140, 2970–2976.
    [Google Scholar]
  57. Zaragoza, C., Ocampo, C., Saura, M., Leppo, M., Wei, X.-Q., Quick, R., Moncada, S., Liew, F. Y. & Lowenstein, C. J. ( 1998; ). The role of inducible nitric oxide synthase in the host response to Coxsackievirus myocarditis. Proc Natl Acad Sci U S A 95, 2469–2474.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82131-0
Loading
/content/journal/jgv/10.1099/vir.0.82131-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error