LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

Abstract

ABSTRACTHost defense peptides are immediate responders of the innate immunity that express antimicrobial, immunoregulatory, and wound-healing activities. Neutrophils are a major source for oral host defense peptides, and phagocytosis by neutrophils is a major mechanism for bacterial clearance in the gingival tissue. Dysfunction of or reduction in the numbers of neutrophils or deficiency in the LL-37 host defense peptide was each previously linked with proliferation of oralAggregatibacter actinomycetemcomitanswhich resulted in an aggressive periodontal disease. Surprisingly,A. actinomycetemcomitansshows resistance to high concentrations of LL-37. In this study, we demonstrated that submicrocidal concentrations of LL-37 inhibit biofilm formation byA. actinomycetemcomitansand act as opsonins and agglutinins that greatly enhance its clearance by neutrophils and macrophages. Improved uptake ofA. actinomycetemcomitansby neutrophils was mediated by their opsonization with LL-37. Enhanced phagocytosis and killing ofA. actinomycetemcomitansby murine macrophage-like RAW 264.7 cells were dependent on their preagglutination by LL-37. AlthoughA. actinomycetemcomitansis resistant to the bactericidal effect of LL-37, our results offer a rationale for the epidemiological association between LL-37 deficiency and the expansion of oralA. actinomycetemcomitansand indicate a possible therapeutic use of cationic peptides for host defense.