Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells.
Rivas-Santiago. Bruno B; Hernandez-Pando. Rogelio R; Carranza. Claudia C; Juarez. Esmeralda E; Contreras. Juan Leon JL; Aguilar-Leon. Diana D; Torres. Martha M; Sada. Eduardo E
Key Findings
- TB infection triggers LL‑37 production in alveolar macrophages, monocytes, neutrophils, and epithelial cells
- LL‑37 is most strongly induced in alveolar macrophages and is absent in mature TB granulomas
- TLR‑2, TLR‑4, and especially TLR‑9 activation (by TB DNA) can up‑regulate LL‑37
Practical Outcomes
- The study suggests that boosting LL‑37 early in TB infection might help the immune response, but it doesn’t provide a clear way to do this in humans. For biohackers, it hints that TLR‑activating supplements (like certain bacterial components or vitamin D, which can raise LL‑37) could be explored, yet no dosage or safety data are given, so any use would be experimental.
Summary
When lung cells get infected with TB bacteria, they quickly make more of the natural antimicrobial peptide LL‑37, especially the alveolar macrophages. This early boost disappears later when granulomas form, and the peptide can be turned on by activating certain Toll‑like receptors (TLR‑2, TLR‑4, TLR‑9).
Abstract
The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells, alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis.
Study Information
pubmed
2007
2007-12-26T00:00:00.000Z
10.1128/iai.01218-07