Between good and evil: Complexation of the human cathelicidin LL-37 with nucleic acids

Claudia Zielke; Josefine Eilsø Nielsen; Jennifer S Lin; Annelise E Barron

doi:10.1016/j.bpj.2023.10.035

Between good and evil: Complexation of the human cathelicidin LL-37 with nucleic acids

Biophys J. 2023 Nov 2:S0006-3495(23)00671-9. doi: 10.1016/j.bpj.2023.10.035. Online ahead of print.

Authors

Claudia Zielke¹, Josefine Eilsø Nielsen², Jennifer S Lin¹, Annelise E Barron³

Affiliations

¹ Department of Bioengineering, Stanford University, Schools of Medicine and of Engineering, Stanford, California.
² Department of Bioengineering, Stanford University, Schools of Medicine and of Engineering, Stanford, California; Department of Science and Environment, Roskilde University, Roskilde, Denmark.
³ Department of Bioengineering, Stanford University, Schools of Medicine and of Engineering, Stanford, California. Electronic address: aebarron@stanford.edu.

PMID: 37919905
DOI: 10.1016/j.bpj.2023.10.035

Abstract

The innate immune system provides a crucial first line of defense against invading pathogens attacking the body. As the only member of the human cathelicidin family, the antimicrobial peptide LL-37 has been shown to have antiviral, antifungal, and antibacterial properties. In complexation with nucleic acids, LL-37 is suggested to maintain its beneficial health effects while also acting as a condensation agent for the nucleic acid. Complexes formed by LL-37 and nucleic acids have been shown to be immunostimulatory with a positive impact on the human innate immune system. However, some studies also suggest that in some circumstances, LL-37/nucleic acid complexes may be a contributing factor to autoimmune disorders such as psoriasis and systemic lupus erythematosus. This review provides a comprehensive discussion of research highlighting the beneficial health effects of LL-37/nucleic acid complexes, as well as discussing observed detrimental effects. We will emphasize why it is important to investigate and elucidate structural characteristics, such as condensation patterns of nucleic acids within complexation, and their mechanisms of action, to shed light on the intricate physiological effects of LL-37 and the seemingly contradictory role of LL-37/nucleic acid complexes in the innate immune response.

Publication types

Review