Cathelicidin antimicrobial peptide LL-37 augments interferon-β expression and antiviral activity induced by double-stranded RNA in keratinocytes

Summary Background Cathelicidin antimicrobial peptide LL‐37 has the capacity to kill a wide range of microbes and to modify host immunity. Recently, our group observed that the activation of keratinocytes by LL‐37 and DNA greatly increases interferon (IFN)‐β through Toll‐like receptor (TLR)9. However, the effect of LL‐37 on the induction of IFN‐β through TLR3, a sensor of double‐stranded (ds) RNA, in keratinocytes is not well known. Objectives To investigate whether LL‐37 could affect TLR3 signalling and antiviral activity in normal human epidermal keratinocytes (NHEKs). Methods We investigated the production of IFN‐β in NHEKs stimulated with a TLR3 ligand, poly (I:C), in the presence of LL‐37. To examine the effect of LL‐37 and poly (I:C) on antiviral activity, a virus plaque assay using herpes simplex (HS) virus type‐1 was carried out. The uptake of poly (I:C) conjugated with fluorescein isothiocyanate (FITC) into the keratinocytes was observed in the presence of LL‐37. Immunostaining for TLR3 and LL‐37 was performed using skin samples from HS. Results LL‐37 and poly (I:C) synergistically induced the expression of IFN‐β in NHEKs. Furthermore, co‐stimulation with LL‐37 and poly (I:C) significantly decreased the viral plaque numbers compared with poly (I:C) or LL‐37 alone. LL‐37 enhanced the uptake of FITC‐conjugated poly (I:C) into cells. Immunohistochemical analysis demonstrated that the expression of TLR3 and LL‐37 is upregulated in HS lesions. Conclusions Our findings suggest that LL‐37 augments the antiviral activity induced by dsRNA in keratinocytes, which may contribute to the innate immune response to cutaneous viral infections such as HS. What's already known about this topic? LL‐37 enhances DNA uptake into intracellular compartments, which leads to Toll‐like receptor (TLR)9‐ and TLR7‐dependent overproduction of interferons (IFNs) in dendritic cells. In keratinocytes, LL‐37 enhances the responsiveness of TLR9. LL‐37 modulates poly (I:C)‐induced proinflammatory responses in keratinocytes. What does this study add? In keratinocytes, LL‐37 enhances the expression of IFN‐β and antiviral activity induced by poly (I:C).