LL-37, also known as cathelicidin antimicrobial peptide, is the only human cathelicidin and represents a cornerstone of innate immunity. This 37-amino-acid peptide gets its name from terminal leucine-leucine (LL) residues and its length. Unlike antimicrobial peptides found in other organisms, LL-37 is uniquely human and produced by neutrophils, macrophages, and epithelial cells.
Structure and Basic Properties
LL-37 is a cationic (positively charged) peptide at physiological pH. This positive charge is fundamental to its mechanism—it allows the peptide to bind to negatively charged bacterial membranes and cell walls. The peptide’s structure consists of hydrophobic and hydrophilic regions, creating an amphipathic molecule capable of inserting into biological membranes.
Primary Mechanism: Direct Antimicrobial Action
LL-37 kills microorganisms through membrane disruption. The peptide binds to bacterial lipopolysaccharides (LPS) and phospholipids, causing:
- Pore formation in bacterial membranes
- Loss of membrane integrity
- Leakage of cellular contents
- Bacterial cell death
This mechanism is broad-spectrum, affecting gram-positive bacteria, gram-negative bacteria, fungi, and certain viruses.
Secondary Mechanism: Immunomodulation via TLR Signalling
Beyond direct killing, LL-37 functions as an immunomodulator. It binds to toll-like receptors (TLRs), particularly TLR3 and TLR9, triggering:
- Dendritic cell activation
- Enhanced antigen presentation
- Promotion of Th1 and Th17 immune responses
- Inflammatory cytokine production (IL-6, TNF-α)
- Recruitment of additional immune cells to infection sites
Production and Regulation
LL-37 is produced constitutively by epithelial cells and immune cells, but production increases dramatically in response to infection, inflammation, or tissue damage. Various stimuli upregulate LL-37 expression, including microbial products, inflammatory cytokines (TNF-α, IL-6), and growth factors. This tight regulation ensures LL-37 appears where needed most.
Physiological Significance
As the only human cathelicidin, LL-37 plays essential roles in:
- First-line antimicrobial defence at mucosal and skin barriers
- Linking innate and adaptive immunity
- Promoting tissue repair and wound healing
- Maintaining tissue homeostasis
Understanding LL-37 function is critical for comprehending how humans defend against infection and maintain tissue health.
🔗 Related Reading: For a comprehensive overview of LL-37 research, see our LL-37 UK: Complete Research Guide (2026).
