Modulation of Adaptive Immune Responses in Chickens by Low Pathogenicity Avian Influenza Virus H9N2 (B142)

Abstract

Abstract Most low pathogenicity avian influenza (LPAI) viruses cause no or mild diseases in avian species. The H9N2 subtype are commonly detected LPAI viruses that have crossed the species barrier to infect humans, unlike most other LPAI viruses. We report in this study that chicken macrophages are susceptible to infection with H9N2 and H6N2 viruses and infection led to apoptosis. Additionally, in H9N2 virus-infected macrophages, major histocompatibility complex (MHC) antigens, class II in particular, were downregulated, which also occurred in the lungs of H9N2 infected chickens. Pro-inflammatory cytokines and chemokines were differentially regulated in both infected macrophages and lungs. Among the regulated genes, IL-4, IL-4R, and CD74 were downregulated, all of which are pivotal in the activation of CD4+ helper T cells and humoral immunity. Remarkably, in H9N2 virus-infected chickens the antibody response was largely suppressed. This is in contrast to what was observed in those infected with H6N2 virus. This finding suggests that the pathogenesis of H9N2 infection in chickens may involve humoral immune suppression. Modulation of MHC antigens and the subsequent impact on the immune responses in mammals infected with avian influenza viruses is largely unclear. These findings raise questions about how some LPAI viruses regulate avian immune responses and if they have similar effects on mammalian immune function.