Systems-based approach to examine the cytokine responses in primary mouse lung macrophages infected with low pathogenic avian Influenza virus circulating in South East Asia

Abstract

Background: Influenza A virus (IAV) is a major public health concern, .being .responsible for the death of approximately half a million people each year. Zoonotic transmissions of the virus from swine and avian origin have occurred in the past, and can potentially lead to the em.gergence of new IAV stains. in fut.ure pandemics. Pulmonary macrophages have been implicated in disease severity in the lower airway, and understanding the host response .of macrophages infected with avian influenza viruses should provide new therapeutic strategies. Results: We used a systems-based approach to investigate the transcriptome response of primary murine lung macrophages (PM) infected with the mouse-adapted H1N1/WSN virus and low pathogenic avian influenza (LPAI) viruses H5N2 and H5N3. The results showed that the LPAI viruses H5N2 and H5N3 can infect PM with similar efficiency to the H1N1/WSN virus. While all viruses induced antiviral responses, the H5N3 virus infection resulted in higher expression levels of cytokines and chemokines associated with inflammatory responses. Conclusions: The LPAI H5N2 and H5N3 viruses are able to infect murine lung macrophages. However, the H5N3 virus was associated with increased expression of pro.-inflammatory mediators. A.lthough. the H5N3 virus it is capable of inducing high levels of cytokines that are associated with inflammation., this property is disti.nct from its inability to. efficiently replicate in a mammalian host.