RETRACTED: The rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model

Abstract

Dendritic cells (DCs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. The aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (LALNs) in the model of a non-human primate (NHP) infected by influenza A virus (IAV). Cynomolgus macaques were infected with influenza A virus (H3N2) via bronchoscopy. Flow cytometry was used to analyze the DC numbers, maturation status and subsets during the time of acute infection (days 1, 2, 3, 4, 7) and the resolution phase (day 30). A dramatic increase in the numbers of influenza A virus-infected CD11c+CD14- myeloid dendritic cells (mDCs) and CD11c-CD123+ plasmacytoid dendritic cells (pDCs) were observed from day 1 to day 4 and peak up from day 7 post-infection. In lung and lung-associated lymph nodes, the numbers and maturation status of myeloid dendritic cells and plasmacytoid dendritic cells increased more slowly than those in the lung tissues. On day 30 post-infection, influenza A virus challenge increased the number of myeloid dendritic cells, but not plasmacytoid dendritic cells, compared with baseline. These findings indicate that dendritic cells are susceptible to influenza A virus infection, with the likely purpose of increasing mature myeloid dendritic cells numbers in the lung and lung and lung-associated lymph nodes, which provides important new insights into the regulation of dendritic cells in a non-human primate model.

H5N1 avian influenza virus without 80–84 amino acid deletion at the NS1 protein hijacks the innate immune system of dendritic cells for an enhanced mammalian pathogenicity

“…For different invaders, DCs can determine the immune bias via different strategy such as cytokines (immune tolerance or immune response), and mobilize other immune-related cells to participate in a broader immune response . Several studies found that H5N1 subtype AIVs have a strong ability to recruit DCs, indicating that DCs play an important role in the formation of "cytokine storm" (Aldridge et al, 2009;Jie et al, 2015;Soloff et al, 2014).…”

The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893–2014

“…The authors identified a core set of genes related to type I interferon responses that were expressed in both species, and other responses that were species- or virus-specific. In another study of host responses to infection, Jie et al studied the response of dendritic cells in the lungs and associated lymph nodes of cynomolgus macaques infected bronchoscopically with an H3N2 virus (Jie et al, 2014). The authors note that humans and macaques possess myeloid and plasmacytoid DCs.…”