Antimicrobial peptide LL-37 promotes bacterial phagocytosis by human macrophages

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• LL-37/hCAP-18 is the sole human cathelicidin, crucial for pathogen defense and immune regulation.
• Understanding LL-37's role in host-pathogen interactions is vital for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the impact of LL-37 on macrophage-mediated bacterial phagocytosis.
• To elucidate the molecular mechanisms underlying LL-37's effect on phagocytosis.

Main Methods:

• Utilized differentiated THP-1 cells and primary human macrophages.
• Assessed bacterial phagocytosis of opsonized and non-opsonized bacteria.
• Analyzed the expression of FcγRs, complement receptors, TLR4, CD14, and FPR2/ALX.
• Employed Cnlp(-/-) and WT mouse macrophages for comparative analysis.

Main Results:

• LL-37 significantly enhanced phagocytosis of both Gram-negative and Gram-positive bacteria in a dose- and time-dependent manner.
• LL-37 upregulated FcγRs, TLR4, and CD14 expression on macrophages.
• FPR2/ALX receptor mediated LL-37-induced phagocytosis, with a concurrent role for TLR4 signaling.
• Macrophages from Cnlp(-/-) mice showed reduced phagocytic capacity compared to wild-type.

Conclusions:

• LL-37 enhances bacterial phagocytosis by macrophages through a mechanism involving FcγRs, FPR2/ALX, and TLR4 signaling.
• This study reveals a novel immune-modulatory function of LL-37 in bacterial clearance.
• LL-37 represents a potential therapeutic target for combating bacterial infections.