1887

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Volume 95, Issue 3

Neutrophils are needed for an effective immune response against pulmonary rat coronavirus infection, but also contribute to pathology Free

Abstract

Polymorphonuclear neutrophils (PMN) infiltrate the respiratory tract early after viral infection and can contribute to both host defence and pathology. Coronaviruses are important causes of respiratory tract infections, ranging from mild to severe depending on the viral strain. This study evaluated the role of PMN during a non-fatal pulmonary coronavirus infection in the natural host. Rat coronavirus (RCoV) causes respiratory disease in adult rats, characterized by an early PMN response, viral replication and inflammatory lesions in the lungs, mild weight loss and effective resolution of infection. To determine their role during RCoV infection, PMN were depleted and the effects on disease progression, viral replication, inflammatory response and lung pathology were analysed. Compared with RCoV infection in control animals, PMN-depleted rats had worsened disease with weight loss, clinical signs, mortality and prolonged pulmonary viral replication. PMN-depleted animals had fewer macrophages and lymphocytes in the respiratory tract, corresponding to lower chemokine levels. Combined with experiments showing that PMN express cytokines and chemokines in response to RCoV-infected alveolar epithelial cells, these findings support a role for PMN in eliciting an inflammatory response to RCoV infection. Despite their critical role in the protection from severe disease, the presence of PMN was correlated with haemorrhagic lesions, epithelial barrier permeability and cellular inflammation in the lungs. This study demonstrated that while PMN are required for an effective antiviral response, they also contribute to lung pathology during RCoV infection.

  • Received:
  • Accepted:
  • Published Online:
© 2014 SGM
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2014-03-01
2024-04-19
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References

  1. Assiri A., Al-Tawfiq J. A., Al-Rabeeah A. A., Al-Rabiah F. A., Al-Hajjar S., Al-Barrak A., Flemban H., Al-Nassir W. N., Balkhy H. H. other authors 2013; Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis 13:752–761 [View Article][PubMed]
     [Google Scholar]
  2. Beauvillain C., Delneste Y., Scotet M., Peres A., Gascan H., Guermonprez P., Barnaba V., Jeannin P. 2007; Neutrophils efficiently cross-prime naive T cells in vivo. Blood 110:2965–2973 [View Article][PubMed]
     [Google Scholar]
  3. Bradley L. M., Douglass M. F., Chatterjee D., Akira S., Baaten B. J. 2012; Matrix metalloprotease 9 mediates neutrophil migration into the airways in response to influenza virus-induced toll-like receptor signaling. PLoS Pathog 8:e1002641 [View Article][PubMed]
     [Google Scholar]
  4. Cervantes-Barragán L., Kalinke U., Züst R., König M., Reizis B., López-Macías C., Thiel V., Ludewig B. 2009; Type I IFN-mediated protection of macrophages and dendritic cells secures control of murine coronavirus infection. J Immunol 182:1099–1106[PubMed] [CrossRef]
     [Google Scholar]
  5. Crowe C. R., Chen K., Pociask D. A., Alcorn J. F., Krivich C., Enelow R. I., Ross T. M., Witztum J. L., Kolls J. K. 2009; Critical role of IL-17RA in immunopathology of influenza infection. J Immunol 183:5301–5310 [View Article][PubMed]
     [Google Scholar]
  6. Denlinger L. C., Sorkness R. L., Lee W. M., Evans M. D., Wolff M. J., Mathur S. K., Crisafi G. M., Gaworski K. L., Pappas T. E. other authors 2011; Lower airway rhinovirus burden and the seasonal risk of asthma exacerbation. Am J Respir Crit Care Med 184:1007–1014 [View Article][PubMed]
     [Google Scholar]
  7. Dienz O., Rud J. G., Eaton S. M., Lanthier P. A., Burg E., Drew A., Bunn J., Suratt B. T., Haynes L., Rincon M. 2012; Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung. Mucosal Immunol 5:258–266 [View Article][PubMed]
     [Google Scholar]
  8. Fujisawa H. 2008; Neutrophils play an essential role in cooperation with antibody in both protection against and recovery from pulmonary infection with influenza virus in mice. J Virol 82:2772–2783 [View Article][PubMed]
     [Google Scholar]
  9. Funk C. J., Manzer R., Miura T. A., Groshong S. D., Ito Y., Travanty E. A., Leete J., Holmes K. V., Mason R. J. 2009; Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response. J Gen Virol 90:2956–2964 [View Article][PubMed]
     [Google Scholar]
  10. Gagneten S., Scanga C. A., Dveksler G. S., Beauchemin N., Percy D., Holmes K. V. 1996; Attachment glycoproteins and receptor specificity of rat coronaviruses. Lab Anim Sci 46:159–166[PubMed]
     [Google Scholar]
  11. Gaunt E. R., Hardie A., Claas E. C., Simmonds P., Templeton K. E. 2010; Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method. J Clin Microbiol 48:2940–2947 [View Article][PubMed]
     [Google Scholar]
  12. Hartshorn K. L., Crouch E. C., White M. R., Eggleton P., Tauber A. I., Chang D., Sastry K. 1994; Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J Clin Invest 94:311–319 [View Article][PubMed]
     [Google Scholar]
  13. Hashimoto Y., Moki T., Takizawa T., Shiratsuchi A., Nakanishi Y. 2007; Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. J Immunol 178:2448–2457[PubMed] [CrossRef]
     [Google Scholar]
  14. Hosking M. P., Liu L., Ransohoff R. M., Lane T. E. 2009; A protective role for ELR+ chemokines during acute viral encephalomyelitis. PLoS Pathog 5:e1000648 [View Article][PubMed]
     [Google Scholar]
  15. Iacono K. T., Kazi L., Weiss S. R. 2006; Both spike and background genes contribute to murine coronavirus neurovirulence. J Virol 80:6834–6843 [View Article][PubMed]
     [Google Scholar]
  16. Ireland D. D., Stohlman S. A., Hinton D. R., Atkinson R., Bergmann C. C. 2008; Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells. J Virol 82:300–310 [View Article][PubMed]
     [Google Scholar]
  17. Janardhan K. S., Sandhu S. K., Singh B. 2006; Neutrophil depletion inhibits early and late monocyte/macrophage increase in lung inflammation. Front Biosci 11:1569–1576 [View Article][PubMed]
     [Google Scholar]
  18. Khanolkar A., Hartwig S. M., Haag B. A., Meyerholz D. K., Harty J. T., Varga S. M. 2009; Toll-like receptor 4 deficiency increases disease and mortality after mouse hepatitis virus type 1 infection of susceptible C3H mice. J Virol 83:8946–8956 [View Article][PubMed]
     [Google Scholar]
  19. Lee N., Hui D., Wu A., Chan P., Cameron P., Joynt G. M., Ahuja A., Yung M. Y., Leung C. B. other authors 2003; A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 348:1986–1994 [View Article][PubMed]
     [Google Scholar]
  20. Leong H. N., Earnest A., Lim H. H., Chin C. F., Tan C. S., Puhaindran M. E., Tan A. C., Chen M. I., Leo Y. S. 2006; SARS in Singapore–predictors of disease severity. Ann Acad Med Singapore 35:326–331[PubMed]
     [Google Scholar]
  21. Li X., Kovacs E. J., Schwacha M. G., Chaudry I. H., Choudhry M. A. 2007; Acute alcohol intoxication increases interleukin-18-mediated neutrophil infiltration and lung inflammation following burn injury in rats. Am J Physiol Lung Cell Mol Physiol 292:L1193–L1201 [View Article][PubMed]
     [Google Scholar]
  22. Liu M. T., Chen B. P., Oertel P., Buchmeier M. J., Armstrong D., Hamilton T. A., Lane T. E. 2000; The T cell chemoattractant IFN-inducible protein 10 is essential in host defense against viral-induced neurologic disease. J Immunol 165:2327–2330[PubMed] [CrossRef]
     [Google Scholar]
  23. Mantovani A., Cassatella M. A., Costantini C., Jaillon S. 2011; Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11:519–531 [View Article][PubMed]
     [Google Scholar]
  24. Mckean M. C., Hewitt C., Lambert P. C., Myint S., Silverman M. 2003; An adult model of exclusive viral wheeze: inflammation in the upper and lower respiratory tracts. Clin Exp Allergy 33:912–920 [View Article][PubMed]
     [Google Scholar]
  25. Miura T. A., Wang J., Holmes K. V., Mason R. J. 2007; Rat coronaviruses infect rat alveolar type I epithelial cells and induce expression of CXC chemokines. Virology 369:288–298 [View Article][PubMed]
     [Google Scholar]
  26. Nagata N., Iwata N., Hasegawa H., Fukushi S., Harashima A., Sato Y., Saijo M., Taguchi F., Morikawa S., Sata T. 2008; Mouse-passaged severe acute respiratory syndrome-associated coronavirus leads to lethal pulmonary edema and diffuse alveolar damage in adult but not young mice. Am J Pathol 172:1625–1637 [View Article][PubMed]
     [Google Scholar]
  27. Ofulue A. F., Ko M. 1999; Effects of depletion of neutrophils or macrophages on development of cigarette smoke-induced emphysema. Am J Physiol 277:L97–L105[PubMed]
     [Google Scholar]
  28. Radsak M., Iking-Konert C., Stegmaier S., Andrassy K., Hänsch G. M. 2000; Polymorphonuclear neutrophils as accessory cells for T-cell activation: major histocompatibility complex class II restricted antigen-dependent induction of T-cell proliferation. Immunology 101:521–530 [View Article][PubMed]
     [Google Scholar]
  29. Rzepka J. P., Haick A. K., Miura T. A. 2012; Virus-infected alveolar epithelial cells direct neutrophil chemotaxis and inhibit their apoptosis. Am J Respir Cell Mol Biol 46:833–841 [View Article][PubMed]
     [Google Scholar]
  30. Sakai S., Kawamata H., Mantani N., Kogure T., Shimada Y., Terasawa K., Sakai T., Imanishi N., Ochiai H. 2000; Therapeutic effect of anti-macrophage inflammatory protein 2 antibody on influenza virus-induced pneumonia in mice. J Virol 74:2472–2476 [View Article][PubMed]
     [Google Scholar]
  31. Scapini P., Lapinet-Vera J. A., Gasperini S., Calzetti F., Bazzoni F., Cassatella M. A. 2000; The neutrophil as a cellular source of chemokines. Immunol Rev 177:195–203 [View Article][PubMed]
     [Google Scholar]
  32. Shibata F., Konishi K., Kato H., Komorita N., al-Mokdad M., Fujioka M., Nakagawa H. 1995; Recombinant production and biological properties of rat cytokine-induced neutrophil chemoattractants, GRO/CINC-2 alpha, CINC-2 beta and CINC-3. Eur J Biochem 231:306–311 [View Article][PubMed]
     [Google Scholar]
  33. Sir O., Fazal N., Choudhry M. A., Gamelli R. L., Sayeed M. M. 2000; Neutrophil depletion prevents intestinal mucosal permeability alterations in burn-injured rats. Am J Physiol Regul Integr Comp Physiol 278:R1224–R1231[PubMed]
     [Google Scholar]
  34. Snipes M. B., Barnett A. L., Harkema J. R., Hotchkiss J. A., Rebar A. H., Reddick L. J. 1995; Specific biological effects of an anti-rat PMN antiserum intraperitoneally infected into f344/n rats. Vet Clin Pathol 24:11–17 [View Article][PubMed]
     [Google Scholar]
  35. Tate M. D., Brooks A. G., Reading P. C. 2008; The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice. Respir Res 9:57 [View Article][PubMed]
     [Google Scholar]
  36. Tate M. D., Deng Y. M., Jones J. E., Anderson G. P., Brooks A. G., Reading P. C. 2009; Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J Immunol 183:7441–7450 [View Article][PubMed]
     [Google Scholar]
  37. Tate M. D., Ioannidis L. J., Croker B., Brown L. E., Brooks A. G., Reading P. C. 2011; The role of neutrophils during mild and severe influenza virus infections of mice. PLoS ONE 6:e17618 [View Article][PubMed]
     [Google Scholar]
  38. Tate M. D., Brooks A. G., Reading P. C., Mintern J. D. 2012; Neutrophils sustain effective CD8(+) T-cell responses in the respiratory tract following influenza infection. Immunol Cell Biol 90:197–205 [View Article][PubMed]
     [Google Scholar]
  39. Tecle T., White M. R., Gantz D., Crouch E. C., Hartshorn K. L. 2007; Human neutrophil defensins increase neutrophil uptake of influenza A virus and bacteria and modify virus-induced respiratory burst responses. J Immunol 178:8046–8052[PubMed] [CrossRef]
     [Google Scholar]
  40. Tsui P. T., Kwok M. L., Yuen H., Lai S. T. 2003; Severe acute respiratory syndrome: clinical outcome and prognostic correlates. Emerg Infect Dis 9:1064–1069 [View Article][PubMed]
     [Google Scholar]
  41. Tumpey T. M., García-Sastre A., Taubenberger J. K., Palese P., Swayne D. E., Pantin-Jackwood M. J., Schultz-Cherry S., Solórzano A., Van Rooijen N. other authors 2005; 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 79:14933–14944 [View Article][PubMed]
     [Google Scholar]
  42. Weir E. C., Jacoby R. O., Paturzo F. X., Johnson E. A., Ardito R. B. 1990; Persistence of sialodacryoadenitis virus in athymic rats. Lab Anim Sci 40:138–143[PubMed]
     [Google Scholar]
  43. West B. C., Escheté M. L., Cox M. E., King J. W. 1987; Neutrophil uptake of vaccinia virus in vitro. J Infect Dis 156:597–606 [View Article][PubMed]
     [Google Scholar]
  44. Widegren H., Andersson M., Borgeat P., Flamand L., Johnston S., Greiff L. 2011; LTB4 increases nasal neutrophil activity and conditions neutrophils to exert antiviral effects. Respir Med 105:997–1006 [View Article][PubMed]
     [Google Scholar]
  45. Wojcinski Z. W., Percy D. H. 1986; Sialodacryoadenitis virus-associated lesions in the lower respiratory tract of rats. Vet Pathol 23:278–286[PubMed]
     [Google Scholar]
  46. Zhou J., Stohlman S. A., Hinton D. R., Marten N. W. 2003; Neutrophils promote mononuclear cell infiltration during viral-induced encephalitis. J Immunol 170:3331–3336[PubMed] [CrossRef]
     [Google Scholar]
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Neutrophils are needed for an effective immune response against pulmonary rat coronavirus infection, but also contribute to pathology
J. Gen. Virol. 95, 578 (2014); https://doi.org/10.1099/vir.0.061986-0
/content/journal/jgv/10.1099/vir.0.061986-0
/content/journal/jgv/10.1099/vir.0.061986-0
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