Comparison of pro-inflammatory cytokine expression and cellular signal transduction in human macrophages infected with different influenza A viruses

• Published in: Medical microbiology and immunology 2011-02, Vol.200 (1), p.53-60
• Main Authors: Geiler, Janina, Michaelis, Martin, Sithisarn, Patchima, Cinatl, Jindrich Jr
• Format: Article
• Language: English
• Subjects: Apoptosis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cell Line; Cytokines; Cytokines - biosynthesis; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; H5N1; Humans; Immunology; Influenza; Influenza A; Influenza A virus; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H5N1 Subtype - immunology; Influenza, Human - immunology; Influenza, Human - pathology; Influenza, Human - virology; Macrophages - virology; MAP Kinase Kinase 4 - metabolism; MAPK; Medical Microbiology; Microbiology; Miscellaneous; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Original Investigation; p38 Mitogen-Activated Protein Kinases - metabolism; Pandemic H1N1/2009; Phosphorylation; Seasonal influenza; Signal Transduction; Viral infections; Virology
• ISSN: 0300-8584; 1432-1831
• DOI: 10.1007/s00430-010-0173-y

Influenza A virus infection of macrophages and virus-induced pro-inflammatory gene expression are regarded to contribute to severity of influenza A virus-caused diseases. Although some data are available on cytokine production by influenza A virus-infected macrophages, systematic comparisons of the virus types are currently considered to be of high relevance in humans (pandemic H1N1/2009, seasonal H1N1, seasonal H3N2, highly pathogenic avian influenza H5N1) on pro-inflammatory potential, and relevant underlying cellular signalling events are missing. Here, we show that the infection of human monocyte-derived macrophages with pandemic H1N1/2009 (A/HH/01/2009), seasonal H1N1/1999 (A/New Caledonia/20/99), seasonal H3N2/2004 (A/California/7/2004) or highly pathogenic H5N1/2004 (A/Thailand/1(Kan-1)/04) results in similar infection rates. However, the investigated H1N1 strains caused delayed and decreased apoptosis in comparison with H3N2/2004 or H5N1/2004. Moreover, human macrophage infection with H3N2/2004 or H5N1/2004 but not with H1N1 viruses was associated with pronounced pro-inflammatory cytokine production and activation of relevant mitogen-activated protein kinase pathways as indicated by phosphorylation of p38, JNK and ERK 1/2. These findings are in line with clinical observations indicating enhanced disease severity in H3N2- or H5N1-infected patients compared to individuals infected with pandemic H1N1/2009 or seasonal H1N1.