However, it would not be appropriate to generalize the results reported here to all major- and minor-group viruses without performing additional confirmatory studies. Our results suggest that there is not a general viral response to HRV but rather that the macrophage responds with a virusspecific signaling response after receptor ligation. It was previously unclear if these differences translated into the development of different inflammatory microenvironments created by the viruses. Our cytokine ELISA data were quite variable, likely because any given population of primary human monocytic cells will be reacting to different immune stimuli. Indeed, Rajan et al. also noted differences in primary human monocytic cells isolated from different subjects. However, a large dataset, focused on a healthy cohort, allowed us to identify statistically significant differences in the expression of CCL20, CCL2 and IL-10, all of which are important during rhinovirus infection and virally induced asthma exacerbations, after exposure with HRV16 and HRV1A. These differences did not extend to the production of CXCL10, which is also known to be involved in immune cell recruitment to sites of infection. Importantly, results obtained via qPCR did not always mirror the trends in expression observed by ELISA. However, as ELISA measures accumulation of protein, whereas qPCR measures expression at discrete time points, it is possible that differential RNA expression at time points that were not directly observed led to cytokine accumulation. The recently discovered HRV-C clade is often associated with severe symptoms and asthma attacks. Although the receptor for HRV-C is as of yet unidentified, the results of this study and our previous study on the Rac/TLR3/ IFN axis suggest several testable hypotheses. The binding of HRV-C to its receptor will trigger activation of signaling pathways described in our studies. The activation of those signaling pathways will in part lead to an altered inflammatory microenvironment. Finally, human monocytic cells will have the receptor on their surface necessary for HRV-C entry. Thus, all clades of rhinovirus will have selected receptors for entry that also trigger certain signaling pathways. This would suggest that monocytic cells, despite being non-permissive to HRV infection play an important role in HRV pathogenesis. With these results, we propose a model wherein three separate factors affect the microinflammatory environment stimulated by HRV with respect to primary human macrophages. First, freshly activated macrophages are not always in a similar state of activation. Each individual is constantly dealing with different immunological changes resulting in isolated macrophages that respond differently to HRV challenge. Thus, a large data set was needed to observe clear differences between HRV treatments at the inflammatory mediator expression level.