Intranasal administration of IL-15c resulted in increased numbers of NK cells in the lung airways that appeared to be due to increased migration into that site. Previous studies have indicated that IL-15 is indeed chemotactic for NK cells. In vitro checkerboard assays revealed that freshly isolated NK cells migrated to IL-15 gradients, and IL-15 stimulation increased LFA-1-dependent binding of NK cells to cultured endothelial cells [25] . IL-15 has also been shown to play a central role in the recruitment of CD16 2 human NK cells into the endometrium following ovulation [36] . To test the direct chemotactic potential of IL-15c for NK cells in our own system, we employed an in vitro chemotaxis transwell assay. Bulk lymphocytes (or purified splenic NK cells, data not shown) from the BAL, lung, and spleen of mice collected three days after infection with influenza were placed in the top chamber of a transwell filter support with either media alone or media supplemented with IL-15c in the bottom chamber. After 90 minutes of incubation, IL-15c significantly enriched NK cells isolated from the lung and spleen ( Figure 4A ). Consistent with our findings with CD8 T cells [19] , NK cells from the lung airways did not migrate to IL-15c, perhaps because this site represents the terminal destination for these cell populations. Unlike CD8 T cells, which lose expression of CD122 upon residence in the lung airways following influenza infection [19] [37] , nearly 100% of the NK cells residing in the BAL of influenza-infected mice express CD122 ( Figure 1A and B) . Nonetheless, these data indicate that NK cells in the lung parenchyma or the general circulation (as represented by the spleen) migrate to IL-15 in vitro. Intranasal administration of IL-15c during the innate phase enhances early viral control A temporal cessation in IL-15 bioavailability reduced the numbers of NK cells (Figure 2A ) in the respiratory tract resulting in increased viral titers ( Figure 2E) , presumably due to impaired NK cell responses. Conversely, exogenous IL-15c promoted the migration of NK cells ( Figure 4 ) and resulted in increased numbers of NK cells in the lung airways ( Figure 3B ). We therefore hypothesized that intranasal administration of IL-15c early after infection could be used to enhance the early innate immune response to influenza and augment viral control. To this end, influenza-infected animals received either PBS or IL-15c intranasally on days 1-4 p.i., a time frame corresponding to the migration of NK cells into the lung airways and limiting any confounding effects IL-15c might have on adaptive immune cells entering the lung airways at later time points. Every other day, from day 2-8 p.i., whole lungs were collected and viral titers were quantified via plaque assay ( Figure 5A ). Early (d2) p.i., we observed no difference in viral load between PBS and IL-15c-treated mice, but as viral replication reached more significant levels at day 4 p.i., animals receiving the IL-15c had 2.46 less viral load than animals receiving only PBS ( Figure 5B and C) . Although viral titers dropped 10 fold in both groups of animals by day 6 p.i., as expected, surprisingly, there remained a greater than 2 fold significant difference in viral load ( Figure 5B and D) . Although both groups of animals cleared the influenza virus completely by day 8 p.i. (Figure 5B ), our data suggest administration of IL-15c on days 1-4 p.i. can enhance early control of influenza virus by cells of the innate immune system.