Abstract

The influenza A viruses (IAVs) cause acute respiratory infection in both humans and animals. As a member of the initial lines of host defense system, the role of mast cells during IAV infection has been poorly understood. Here, we characterized for the first time that both avian-like (α-2, 3-linked) and human-like (α-2, 6- linked) sialic acid (SA) receptors were expressed by the mouse mastocytoma cell line (P815). The P815 cells did support the productive replication of H1N1 (A/WSN/33), H5N1 (A/chicken/ Henan/1/04) and H7N2 (A/chicken/Hebei/2/02) in vitro while the in vivo infection of H5N1 in mast cells was confirmed by the specific staining of nasal mucosa and lung tissue from mice. All the three viruses triggered the infected P815 cells to produce pro-inflammatory cytokines and chemokines including IL-6, IFN-γ, TNF-α, CCL-2, CCL-5, and IP-10, but not the antiviral type I interferon. It was further confirmed that TLR3 pathway was involved in P815 cell response to IAV-infection. Our findings highlight the remarkable tropism and infectivity of IAV to P815 cells, indicating that mast cells may be unneglectable player in the development of IAV infection.

Highlights

  • Influenza A virus (IAV) is one of the most common respiratory pathogen in humans and animals

  • Mast cells, an important cell type in the first lines of host immunity and defense, have been largely overlooked until recently, data from our lab and others have demonstrated a possible involvement of mast cells in IAV infection (Hu et al, 2012; Graham et al, 2013; Marcet et al, 2013)

  • Our previous study showed that mast cells actively participate in the firstline immunological responses to IAV infection

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Summary

Introduction

Influenza A virus (IAV) is one of the most common respiratory pathogen in humans and animals. Since the first outbreak in Hong Kong in 1997, the highly pathogenic avian influenza (HPAI) H5N1 virus has become a public health threat due to its potential to cause serious illness and death in humans (Uyeki, 2009). Virus-induced acute lung injury or its more severe form, acute respiratory distress syndrome (ARDS), is a major cause of mortality by pandemic influenza and HAPI H5N1 infections; the exact mechanism of this injury is not fully understood. IAV Replicate in P815 Cells cytokines or “cytokine storm” (Thuy et al, 2011). This response may result from each individual cell producing more cytokines, or through chemokines-induced recruitment of a greater number of innate immune cells into the lung (Teijaro et al, 2011). The cellular sources involved in the resulting cytokine storm remain undetermined

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