Synthetic cathelicidin LL-37 reduces Mycobacterium avium subsp. paratuberculosis internalization and pro-inflammatory cytokines in macrophages.
Cirone. Karina M KM; Lahiri. Priyoshi P; Holani. Ravi R; Tan. Yi Lin YL; Arrazuria. Rakel R; De Buck. Jeroen J; Barkema. Herman W HW; Cobo. Eduardo R ER
Key Findings
- Synthetic LL‑37 lowered the amount of MAP bacteria inside mouse macrophage cells.
- Treatment reduced the gene activity of pro‑inflammatory cytokines TNF‑α and IFN‑γ, while increasing the chemoattractant IL‑8.
- LL‑37 also decreased expression of Toll‑like receptor 2, a molecule that helps mycobacteria invade cells.
Practical Outcomes
- For biohackers, the study suggests LL‑37 has antimicrobial and anti‑inflammatory effects in a controlled lab setting, but there’s no clear guidance on how to use it safely in humans. Until human trials are done, it remains a research tool rather than a ready‑to‑apply supplement or therapy.
Summary
A lab study showed that a synthetic version of the human peptide LL‑37 can help mouse immune cells clear a cattle‑related bacterial infection (MAP) and lower some inflammatory signals. The work is done in cell culture, not in people, and it doesn’t give a dosing plan or safety data for human use.
Abstract
Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic diarrheic intestinal infections in domestic and wild ruminants (paratuberculosis or Johne's disease) for which there is no effective treatment. Critical in the pathogenesis of MAP infection is the invasion and survival into macrophages, immune cells with ability to carry on phagocytosis of microbes. In a search for effective therapeutics, our objective was to determine whether human cathelicidin LL-37, a small peptide secreted by leuckocytes and epithelial cells, enhances the macrophage ability to clear MAP infection. In murine (J774A.1) macrophages, MAP was quickly internalized, as determined by confocal microscopy using green fluorescence protein expressing MAPs. Macrophages infected with MAP had increased transcriptional gene expression of pro-inflammatory TNF-α, IFN-γ, and IL-1β cytokines and the leukocyte chemoattractant IL-8. Pretreatment of macrophages with synthetic LL-37 reduced MAP load and diminished the transcriptional expression of TNF-α and IFN-γ whereas increased IL-8. Synthetic LL-37 also reduced the gene expression of Toll-like receptor (TLR)-2, key for mycobacterial invasion into macrophages. We concluded that cathelicidin LL-37 enhances MAP clearance into macrophages and suppressed production of tissue-damaging inflammatory cytokines. This cathelicidin peptide could represent a foundational molecule to develop therapeutics for controlling MAP infection.
Study Information
pubmed
2019
2019-09-02T00:00:00.000Z
10.1007/s00441-019-03098-4
1