Differential Activation of NK Cells by Influenza A Pseudotype H5N1 and 1918 and 2009 Pandemic H1N1 Viruses

Mast Cell-Induced Lung Injury in Mice Infected with H5N1 Influenza Virus

“…In the present study, we demonstrated that mast cells released a high level of IFN-␥ after H5N1 virus infection in vitro, and this is believed to be the first report that IFN-␥ can be produced by activated mast cells, in addition to T and NK cells, in H5N1 virus infection. Furthermore, many data have shown that IFN-␥ can induce apoptosis of pulmonary epithelial cells, immune cells, and tumor cells (12,27,37,39,46). Our results suggested that activated mast cells probably promoted apoptosis of the pulmonary epithelial cells by releasing IFN-␥.…”

“…For example, mast cells may provide a viral reservoir that can be reactivated by stimuli, such as Toll-like-receptormediated signaling in HIV infection (40). Previous studies have demonstrated that H5N1 influenza virus infection causes a severe inflammatory response in the lung, accompanied by infiltration of various inflammatory cells, including lymphocytes, neutrophils, eosinophils, macrophages, NK cells, and plasmacytes (12,44,45). As far as we are aware, the present study is the first to demonstrate the direct involvement of mast cells in H5N1 infection, showing increased mast cell numbers in the nasal mucosa, trachea, and lungs during the early stage of infection with H5N1 influenza virus in mice.…”

“…Macrophages contribute to the unusual severity of human H5N1 disease by producing tumor necrosis factor alpha (TNF-␣) and other cytokines (9). More recently, a study conducted by Du et al has demonstrated that natural killer (NK) cell activation can be triggered by H5N1-pseudotyped particles (12). Overproduction of inflammatory cytokines, such as TNF-␣, interleukin 6 (IL-6), and CC chemokine ligand 2 (CCL2), has also been demonstrated in H5N1-infected mice or humans, and the "cytokine storm" has been widely hypothesized to be the main cause of pathology and, ultimately, of death (9,26,41).…”

The interaction of influenza H5N1 viral hemagglutinin with sialic acid receptors leads to the activation of human γδ T cells

“…CD69 is a sensitive and very early marker of leukocyte activation. 24,25 Following exposure to the different rHA proteins from different strains, the percentages of CD69 1 cd T cells reached approximately 60%-70%, representing a twofold increase compared to the control (Figure 2a and b). The expression of CD25 was also slightly upregulated following stimulation with the rHA proteins (Figure 2a and c).…”

The Pathogenicity and Host Immune Response Associated with H5N1 Highly Pathogenic Avian Influenza Virus in Quail

“…IFN-γ has antiviral activity through activation of innate immune cells such as macrophages and NK cells [6]. Because these cells are reported to play essential roles in the control of influenza virus [14], IFN-γ is also thought to be associated with the pathogenesis of influenza [3,10]. For example, H5N1 HPAIV was found to induce IFN-γ in mammals [4], and early administration of exogenous IFN-γ during influenza virus infection stimulates NK cell proliferation and function in infected lungs [24].…”