Antimicrobial peptide LL-37 increases rhinovirus-induced interferon β expression in human airway epithelial cells through a Ca-dependent mechanism.

The human cathelicidin LL-37 is active against both bacteria and viruses, but it also shows immunomodulatory properties. Here, we assess the impact of LL-37 on viral signaling in human airway epithelial BEAS-2B cells infected with the respiratory pathogen rhinovirus (RV). We show that LL-37 (4 μM) enhances RV-induced expression of interferon β (IFNβ) transcript and reduces viral-load. LL-37-evoked potentiation of RV-stimulated IFNβ does not involve up-regulation of the classical viral TLR3, MDA5 and RIG-I receptors. Moreover, the LL-37-induced stimulation of IFNβ expression in the presence of RV is abolished by chloroquine, an inhibitor of endosomal acidification. Interestingly, RV + LL-37-induced stimulation of IFNβ is observed in the absence but not in the presence of the Cachelating agent EGTA, indicating that Cais critical for this effect. Indeed, we demonstrate that LL-37 increases intracellular [Ca] in cells loaded with the fluorescent Caindicator Fluo-4 AM. Furthermore, we reveal that treatment with RV in combination with the Caionophore A23187 promotes IFNβ expression, showing the importance of Ca. In conclusion, we demonstrate that LL-37 acts in synergy with RV to enhance IFNβ expression and that this effect involves LL-37-induced increase in intracellular [Ca].