Epithelial cell polarity and differential localization of TLRs on the apical and basolateral cell surface also has been shown to play a role in TLR sensitivity as the apical surface of epithelial cells is more likely to encounter bacteria in the normal state, whereas the basolateral surface of epithelial cells may be more likely to encounter TLR ligands only in states of disease. In support of this concept, TLR4 and TLR2 are expressed at the apical pole of T84 cells and redistribute to a cytoplasmic compartment near the basal pole with activation (77) . Furthermore, differential TLR9 signaling has been shown in colonic HCA-7 epithelial cells. Apical TLR9 activation leads to attenuation of activation of NF-κB pathways, whereas basolateral TLR9 activation leads to activation of NF-κB signaling (91) . In the pulmonary system, TLR2 was located at the apical pole of airway epithelial cells, and increased surface expression was observed in response to bacteria, whereas TLR4 was noted predominately in a basolateral location (160) . In a recent finding by Soong et al., TLR2 became enriched in lipid rafts on the apical surface after bacterial infection in airway epithelial cells, suggesting a role in the regulation of TLR sensitivity (197) .