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.

Immune response in the duck intestine following infection with low-pathogenic avian influenza viruses or stimulation with a Toll-like receptor 7 agonist administered orally

“…This suggested that the level of type I IFN production correlates with viral load in the duck ileum. A similar correlation between viral load and IFN-a levels has been shown recently in the respiratory tract of chickens infected with an LPAI influenza virus (Reemers et al, 2010). It is well known that influenza viruses antagonize type I IFN synthesis by infected cells through multiple actions of the NS1 protein (Hale et al, 2008;Kochs et al, 2007).…”

Enhanced immune response of BMDCs pulsed with H9N2 AIV and CpG

“…Although some research has focused on the interaction between CpG and DCs in vitro, less work has cantered on DCs co-stimulated with CpG and active or inactive H9N2 [8,9]. Thus, exploring the mechanisms involved in recognition of influenza virus (active or inactive) by DCs and enhancement of the immune response by CpG may greatly accelerate vaccine development [10,11].…”

Short- and long-term protective efficacy against clade 2.3.4.4 H5N2 highly pathogenic avian influenza virus following prime-boost vaccination in turkeys

“…Differences in age at time of challenge between studies may account for such discrepancy, which warrant further investigation. It is well established that the age of birds at infection can influence the severity of disease caused by influenza viruses in different avian species [33–35]. Likewise, age-dependent resistance to disease may be associated to differences in immune function and early host responses [33–35].…”

“…It is well established that the age of birds at infection can influence the severity of disease caused by influenza viruses in different avian species [33–35]. Likewise, age-dependent resistance to disease may be associated to differences in immune function and early host responses [33–35]. The Group 1 (Un) 16-week old turkeys showed higher virus levels in tracheal swabs at 2 dpc than the same group at 6-weeks of age.…”