LL-37 prevents infection spread through antimicrobial action, immune modulation, and killing of infected host cells | Research

The takeaway

LL-37 prevents infection spread through three mechanisms: direct antimicrobial killing, immunomodulation via endotoxin neutralization and chemotaxis, and cytotoxic elimination of infected host cells at concentrations found naturally at infection sites.

Three-mechanism defense
LL-37 prevents infection spread through direct killing, immune modulation, AND elimination of infected host cells—a comprehensive innate defense strategy

What the researchers found

Three mechanisms: (1) direct antimicrobial (bacteria + viruses); (2) immunomodulation (endotoxin neutralization, chemotaxis, Ca2+ signaling, both pro/anti-inflammatory); (3) cytotoxicity to infected host cells (1-10 µM). Natural concentrations: up to 300 µM in psoriasis, 1 µM in periodontitis.

Why it matters

Understanding LL-37's triple mechanism provides a comprehensive model for innate antimicrobial defense and informs both LL-37-based therapeutic development and understanding of when LL-37 may cause tissue damage.

How the study worked

Updated narrative review of LL-37 mechanisms in infection containment.

What this study cannot tell us

Review format. In vivo concentrations may vary. The balance between beneficial and harmful LL-37 effects is context-dependent and not fully understood.

How to read the evidence

Updated narrative review synthesizing mechanistic evidence.

When this study was published

Published in 2025.

The bigger picture

LL-37's ability to kill infected host cells—in addition to pathogens directly—represents a "scorched earth" defense strategy. Understanding when this is beneficial versus harmful (e.g., in autoimmune disease) is key to therapeutic development.

Questions still open

At what point does LL-37's host cell killing become pathological?
Could LL-37 analogues be designed to retain antimicrobial but reduce cytotoxic effects?
Does LL-37 deficiency predispose to infection spread?

Common questions

How does LL-37 fight infection?

Through three mechanisms: (1) directly killing bacteria and viruses by disrupting their membranes; (2) recruiting and activating immune cells while neutralizing bacterial toxins; and (3) killing host cells that are already infected, preventing them from being used by pathogens to spread. This triple action makes it a comprehensive first-line defense.

Can LL-37 cause tissue damage?

Yes—at the high concentrations found at infection sites (up to 300 µM in psoriasis), LL-37 can kill both pathogens AND host cells. This is beneficial when it eliminates infected cells, but can cause tissue damage in chronic inflammatory conditions. The balance between protection and damage depends on context.

Read the original research

Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiple mechanisms: an update.

Inflammation research : official journal of the European Histamine Research Society ... [et al.], 74(1), 36

View on PubMed ↗Publisher’s paper ↗

Citation

Svensson, Daniel; Nilsson, Bengt-Olof. (2025). Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiple mechanisms: an update.. Inflammation research : official journal of the European Histamine Research Society ... [et al.], 74(1), 36. https://doi.org/10.1007/s00011-025-02005-8