This study is the first to demonstrate that rotavirus, a segmented dsRNA virus, directly induces IFNa and IFNb production by primary human pDCs. While it has previously been reported that exposure to rotavirus induces IFNa secretion by murine FLT3 ligand-driven pDCs [39] and total human PBMCs [42] , and that this response required pDCs [42] , it was unclear until now whether pDCs produced IFNa directly in response to virus, or if pDCs amplified IFNa production in response to type I IFN or some other signal from a non-pDC. In a limited number of experiments, Mesa et al [42] observed not only pDCs singly positive for IFNa or rotavirus, but also cells double-positive for rotavirus and IFNa at a greater frequency than that reported here. It is important to note that Mesa et al used NSP4 as a marker for rotavirus infection. Extracellular NSP4 has been identified on uninfected cells [61] . Conversely, NSP2, employed in this report, to date has only been detected intracellularly. As such, the percentage of cells identified as positive for rotavirus on the basis of NSP4 staining could be inflated versus those expressing NSP2, as NSP4 staining may include pDCs not truly supporting viral replication; in turn, the percent of NSP4 + IFNa + pDCs would be artificially increased. This, combined with differences in sample size, may explain the discrepancies in the incidence of NSP4 + IFNa + pDCs (n = 3) observed by Mesa et al and the frequency of NSP2 + IFNa + pDCs (n = 27) reported here.