title: Early host responses to avian influenza A virus are prolonged and enhanced at transcriptional level depending on maturation of the immune system.
abstract: Newly hatched chickens are more susceptible to infectious diseases than older birds because of an immature immune system. The aim of this study was to determine to what extent host responses to avian influenza virus (AIV) inoculation are affected by age. Therefore, 1- and 4-week (wk) old birds were inoculated with H9N2 AIV or saline. The trachea and lung were sampled at 0, 8, 16 and 24h post-inoculation (h.p.i.) and gene expression profiles determined using microarray analysis. Firstly, saline controls of both groups were compared to analyse the changes in gene profiles related to development. In 1-wk-old birds, higher expression of genes related to development of the respiratory immune system and innate responses were found, whereas in 4-wk-old birds genes were up regulated that relate to the presence of higher numbers of leukocytes in the respiratory tract. After inoculation with H9N2, gene expression was most affected at 16 h.p.i. in 1-wk-old birds and at 16 and 24h.p.i. in 4-wk-old birds in the trachea and especially in the lung. In 1-wk-old birds less immune related genes including innate related genes were induced which might be due to age-dependent reduced functionality of antigen presenting cells (APC), T cells and NK cells. In contrast cytokine and chemokines gene expression was related to viral load in 1-wk-old birds and less in 4-wk-old birds. Expression of cellular host factors that block virus replication by interacting with viral factors was independent of age or tissue for most host factors. These data show that differences in development are reflected in gene expression and suggest that the strength of host responses at transcriptional level may be a key factor in age-dependent susceptibility to infection, and the cellular host factors involved in virus replication are not.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands. s.reemers@uu.nl
authors.forename: Sylvia S
authors.initials: SS
authors.lastname: Reemers
authors.forename: Dik
authors.initials: D
authors.lastname: van Leenen
authors.forename: Marian J Groot
authors.initials: MJ
authors.lastname: Koerkamp
authors.forename: Daphne
authors.initials: D
authors.lastname: van Haarlem
authors.forename: Peter
authors.initials: P
authors.lastname: van de Haar
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: Lonneke
authors.initials: L
authors.lastname: Vervelde
mesh_terms: D000367:Age Factors; D000818:Animals; D002645:Chickens / Q000235:genetics* / Q000254:growth & development / Q000821:virology*; D016207:Cytokines / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D054884:Host-Pathogen Interactions; D007107:Immune System / Q000254:growth & development*; D007109:Immunity / Q000235:genetics; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics / Q000502:physiology*; D005585:Influenza in Birds / Q000235:genetics / Q000821:virology; D007958:Leukocyte Count; D008168:Lung / Q000254:growth & development / Q000378:metabolism* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D011201:Poultry Diseases / Q000235:genetics / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000254:growth & development / Q000378:metabolism / Q000821:virology
chemical_list: D016207:Cytokines