title: Highly pathogenic avian influenza H5N1 virus induces cytokine dysregulation with suppressed maturation of chicken monocyte-derived dendritic cells.
abstract: One of the major causes of death in highly pathogenic avian influenza virus (HPAIV) infection in chickens is acute induction of pro-inflammatory cytokines (cytokine storm), which leads to severe pathology and acute mortality. DCs and respiratory tract macrophages are the major antigen presenting cells that are exposed to mucosal pathogens. We hypothesized that chicken DCs are a major target for induction of cytokine dysregulation by H5N1 HPAIV. It was found that infection of chicken peripheral blood monocyte-derived dendritic cells (chMoDCs) with H5N1 HPAIV produces high titers of progeny virus with more rounding and cytotoxicity than with H9N2 LPAIV. Expression of maturation markers (CD40, CD80 and CD83) was weaker in both H5N1 and H9N2 groups than in a LPS control group. INF-α, -β and -γ were significantly upregulated in the H5N1 group. Pro-inflammatory cytokines (IL-1β, TNF-α and IL-18) were highly upregulated in early mid (IL-1), and late (IL-6) phases of H5N1 virus infection. IL-8 (CXCLi2) mRNA expression was significantly stronger in the H5N1 group from 6 hr of infection. TLR3, 7, 15 and 21 were upregulated 24 hr after infection by H5N1 virus compared with H9N2 virus, with maximum expression of TLR 3 mRNA. Similarly, greater H5N1 virus-induced apoptotic cell death and cytotoxicity, as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and lactate dehydrogenase assays, respectively, were found. Thus, both H5N1 and H9N2 viruses evade the host immune system by inducing impairment of chMoDCs maturation and enhancing cytokine dysregulation in H5N1 HPAIV-infected cells.
authors.affiliation: ICAR-National Institute of High Security Animal Diseases, Anand Nagar, Bhopal-462022, Madhya Pradesh, India. kalai_82vetmic@yahoo.co.in.
authors.forename: Semmannan
authors.initials: S
authors.lastname: Kalaiyarasu
authors.affiliation: ICAR-National Institute of High Security Animal Diseases, Anand Nagar, Bhopal-462022, Madhya Pradesh, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: ICAR-National Institute of High Security Animal Diseases, Anand Nagar, Bhopal-462022, Madhya Pradesh, India.
authors.forename: Dhanapal
authors.initials: D
authors.lastname: Senthil Kumar
authors.affiliation: ICAR-National Institute of High Security Animal Diseases, Anand Nagar, Bhopal-462022, Madhya Pradesh, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly-243122, Uttar Pradesh, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Dash
authors.affiliation: ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly-243122, Uttar Pradesh, India.
authors.forename: Sushant
authors.initials: S
authors.lastname: Bhat
authors.affiliation: ICAR-National Institute of High Security Animal Diseases, Anand Nagar, Bhopal-462022, Madhya Pradesh, India.
authors.forename: Rohit K
authors.initials: RK
authors.lastname: Khetan
authors.affiliation: ICAR-National Institute of High Security Animal Diseases, Anand Nagar, Bhopal-462022, Madhya Pradesh, India.
authors.forename: Shanmugasundaram
authors.initials: S
authors.lastname: Nagarajan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002645:Chickens; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D005585:Influenza in Birds / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D019562:Viral Load
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors
keywords: avian influenza; chemokine; cytokine; monocyte-derived DC