Thus, influenza infection had no influence on expression of these inhibitory receptors on lung NK cells. CD107a is associated with stored intracellular cytolytic granules in NK cells [29, 30]. CD107a appears at the NK-cell surface when they degranulate their cytolytic contents as a result of activation. Thus, NK-cell degranulation activity is estimated by CD107a expression [29, 30]. NK cells also can produce IFN-γ when activated [31]. Furthermore, treatment with IFN-γ can protect mice from death in a NK-cell-dependent manner at an early stage of influenza infection [32]. We purified lymphocytes from influenza-infected

lung using Percoll gradients, then selleck inhibitor stained the cells with anti-CD3 to exclude T cells and identified those which were NK1.1+, CD122hi, 2B4+, and NKp46+, and therefore likely to be NK cells. We found that a small percentage of these cells were positive for CD107a or IFN-γ (Fig. 2C and D), which was slightly more than by these cells

in uninfected mice (data not shown). By contrast, a CD3−NK1.1+CD122hi2B4+NKp46− population showed extensive Selleckchem GSK458 degranulation (over 90% of the cells), and nearly 15% of this population expressed intracellular IFN-γ during influenza infection (Fig. 2C and D). Cells that lacked CD3, expressed the other NK-cell markers, NK1.1, CD122hi, and 2B4, but not NKp46, were not found in any quantity in uninfected mice (data not shown). Downregulation of NKp46 has been described for human NK cells upon encountering influenza virus in vitro, or after in vivo exposure to influenza [33]. Our results suggest that this may also be the case for NKp46 expressed on mouse NK cells isolated from influenza-infected mice. Thus, it is possible that the CD3−NK1.1+CD122hi2B4+NKp46− cells found in influenza-infected lungs are NK cells that have encountered influenza virus and

have responded with substantial degranulation Astemizole and production of IFN-γ. The NK cells in influenza virus infected lung displayed an activated phenotype, suggesting that they play an active not passive role during influenza infection. To investigate the influence of NK cells on host outcome during influenza infection, we treated mice with anti-asialo GM1 to deplete NK cells in vivo prior to and during influenza infection. Anti-asialo GM1 is effective at depletion of NK cells in vivo [34, 35], as confirmed by our flow cytometric analysis of lung and spleen (Fig. 3A). Interestingly, compared with PBS control mice, depletion of NK cells improved the survival rate (Fig. 3B) and recovery of body weight (Fig. 3C) of surviving animals after influenza virus infection. These results suggested that NK cells may exacerbate pathology induced by influenza infection, leading to a worsened outcome. Our results (Fig. 3) are contradictory to previous reports [24-26] that found that depletion of NK cells increased mouse morbidity and mortality from influenza infection.