Influenza A Viruses Replicate Productively in Mouse Mastocytoma Cells (P815) and Trigger Pro-inflammatory Cytokine and Chemokine Production through TLR3 Signaling Pathway

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.

iTRAQ‐based proteomic and bioinformatic characterization of human mast cells upon infection by the influenza A virus strains H1N1 and H5N1

“…Furthermore, MCs release type I interferons and C-X-C motif chemokine following toll-like receptor 3 activation. These data confirmed that viruses replicate in MC and this virus-MC interaction essentially contributes to the pathogenesis of influenza viruses [10]. However, the detailed response of MCs to these influenza viruses is incompletely understood.…”

“…Research has confirmed that MCs may lack critical factors essential for the replication of H1N1 [9]. However, in our study we found that P815 cells expressed both a-2, 3-and a-2, 6-linked SA receptors to initiate IAV (H1N1, H5N1, and H7N2) infection [10]. Furthermore, MCs release type I interferons and C-X-C motif chemokine following toll-like receptor 3 activation.…”

Non‐IgE mediated mast cell activation

“…TLR3 engagement in mouse and human MCs does not induce degranulation but can inhibit degranulation in some experimental settings . TLR3‐mediated MC activation elicits the production of type I interferon (IFNα/β), IL‐6, TNFα, IFNγ and the chemokines CCL2, CCL4, CCL5, CXCL1, CXCL2, and CXCL10 . This profile of secretion allows MCs to recruit pro‐inflammatory cells such as CD8 + T cells .…”

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“…Since then, it has become well known for its potential to cause global pandemics in humans and mammals at all ages with considerable risks of morbidity and high fatality rates; it is now considered a growing threat to public health around the world. 45,46 To date, it has been classified as a List A disease by the World Organisation for Animal Health (OIE) and as a Category 1 animal disease in China. A variety of antiviral drugs and vaccines have been adopted to prevent and control influenzainduced illness.…”