Morphofunctional status and the role of mononuclear phagocyte system lung compartment in the pathogenesis of influenza A (H5N1) in mammals
- 1 FSBI Research Center of Clinical and Experimental Medicine, Siberian Branch of the Russian Academy of Medical Sciences, No- vosibirsk, Russia
- 2 FSBI Research Center of Clinical and Experimental Medicine, Siberian Branch of the Russian Academy of Medical Sciences, No- vosibirsk, Russia
- 3 FSBI Research Center of Clinical and Experimental Medicine, Siberian Branch of the Russian Academy of Medical Sciences, No- vosibirsk, Russia
- 4 FSBI Research Center of Clinical and Experimental Medicine, Siberian Branch of the Russian Academy of Medical Sciences, No- vosibirsk, Russia
Abstract
Influenza and other respiratory viral infections account for 80%-90% of infectious pathologies. Influenza A (H5N1) virus has an apparent pneumotropism, and therefore the lung compartment of mononuclear phagocyte system plays an important role in antiviral immunity. Lung macrophages are active phagocytes expressing variety of antiviral factors. The investigation of morphofunctional status of lung macrophages and evaluation of their role in mammal antiviral response in a mouse model were performed within the study. Methods: Light microscopy using standard hematoxylin-eosin, and Van-Gizon’s picrofuchsin staining. Immunohistochemistry using influenza A antigen marker specific primary antibodies, myeloperoxidase, cathepsin D, lysozyme, NO synthase, pro-inflammatory cytokines, cells of CD68 macrophage lineage, PCNA proliferative activity. Morphometric and statistical analysis. Results: Influenza A virus antigen was detected in lung macrophages starting from day 1 to day 14 of infection which corresponds with the beginning of convalescence and may be suggestive of prolonged persistence of virus. On the one hand, the cytopathic effects of the virus lead to lung macrophages death mainly via apoptosis through activation of caspase cascade, including caspase-3 and caspase-9. On the other hand, the observed activation of PCNA proliferation marker, perhaps, allows to support the pool of lung macrophages not only by their recruitment from bone marrow but also by their proliferation in situ . The increase of mononuclear phagocyte system cells expressing antiviral factors depended on the stage of infection. In the early stage, there was an increase of number of cells expressing lysozyme, myeloperoxidase, cathepsin D, endothelial NO synthase (eNOS) followed by the increase of number of macrophages expressing inducible NO synthase (iNOS), pro-inflammatory cytokines and interleukins.
- Wilks, S., de Graaf, M., Smith, D.J. and Burke, D.F. (2012) Review of influenza haemagglutinin receptor binding as it relates to pandemic properties. Vaccine, 30, 4369-4376. http://dx.doi.org/10.1016/j.vaccine.2012.02.076
- Hill, A.W., Guralnick, R.P., Wilson, M.J., Habib, F. and Janies, D. (2009) Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza. Infection, Genetics and Evolution, 9, 169-178. http://dx.doi.org/10.1016/j.meegid.2008.10.006
- Kriegova, E., Melle, C., Kolek, V., Hutyrova, B., Mrazek, F., Bleul, A., du Bois, R.M., von Eggeling, F. and Petrek, M. (2006) Protein profiles of bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis. American Journal of Respiratory and Critical Care Medicine, 173, 1145-1154. http://dx.doi.org/10.1164/rccm.200507-1126OC
- Laidlaw, B.J., Decman, V., Ali, M.A., Abt, M.C., Wolf, A.I., Monticelli, L.A., Mozdzanowska, K., Angelosanto, J.M., Artis, D., Erikson, J. and Wherry, E.J. (2013) Cooperativity between CD8+ T cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity. PLOS Pathogens, 9, e1003207. http://dx.doi.org/10.1371/journal.ppat.1003207
- Hashimoto, Y., Moki, T., Takizawa, T., Shiratsuchi, A. and Nakanishi, Y. (2007) Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. Immunology, 178, 2448-2457.
- Tumpey, T.M., Garcia-Sastre, A., Taubenberger, J.K., Palese, P., Swayne, D.E., Pantin-Jackwood, M.J., SchultzCherry, S., Solórzano, A., Van Rooijen, N., Katz, J.M. and Basler, C.F. (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. Journal of Virology, 79, 14933-14944. http://dx.doi.org/10.1128/JVI.79.23.14933-14944.2005
- Nakamura, S. and Kohno, S. (2012) Anti-influenza virus agent. Nihon Rinsho, 70, 568-573.
- Shestopalov, A.M, Sharshov, K.A, Zaykovskaya, A.V., Rassadkin, Y.N., Drozdov, I.G., Shkurupy, V.A., Potapova, O.V. and Luzgina, N.G. (2008) Studying the pathogenicity of avian influenza virus subtype H5N1 strains from the Russian Federation using mouse model. Bulletin of Experimental Biology and Medicine, 146, 341-343. http://dx.doi.org/10.1007/s10517-008-0296-y
- Weibel, E.R. (1963) Morphometry of the human lung. Berlin, Springer, 50-76.
- Shestopalova, L.V., Shkurupy, V.A., Sharkova, Т.V. and Shestopalov A.M. (2008) Morphological changes in bird viscera in experimental infection by highly pathogenic H5N1 avian influenza virus. Bulletin of Experimental Biology and Medicine, 146, 770-773.