Immunomodulatory Effects of the Antimicrobial Peptide KR-20: Implications for Trichomoniasis.

Trichomoniasis is the most prevalent non-viral sexually transmitted infection worldwide and is caused by. The development of resistance against the standard treatment, metronidazole, highlights the need for alternative therapeutic approaches. The role of innate immune cells is crucial for understanding trichomoniasis; however, the contribution of monocytes remains poorly characterized. We previously reported that the antimicrobial peptides LL-37 and its derivative KR-20 are trichomonacidal. In other systems, LL-37 displays immunomodulatory effects. Nevertheless, whether these peptides modulate monocyte responses in the presence ofremains unknown, which was the aim of this study. U937 monocytes were co-incubated with LL-37 or KR-20 (3 h), with or without parasite. Monocyte metabolic activity, nitric oxide production, and relative expression of innate immune genes were assessed. LL-37 decreased monocyte metabolic activity and upregulated TNF-α expression (10 and 5 μM, respectively) in parasite-challenged monocytes. Meanwhile, KR-20 (2.5-10 μM) preserved metabolic activity, bound microbial components (LPS), reduced parasite-induced nitric oxide production, and downregulated the expression of IL-8, TNF-α, IL-1β, and COX-2 in infected monocytes. This work provides initial evidence that KR-20 modulates innate immune response in monocytes duringinfection, suggesting its potential-yet to be fully validated-as an immunomodulatory candidate for trichomoniasis.