IL-27 inhibits anti- Mycobacterium tuberculosis innate immune activity of primary human macrophages.
Gollnick. Hailey H; Barber. Jamie J; Wilkinson. Robert J RJ; Newton. Sandra S; Garg. Ankita A
Key Findings
- IL‑27 is produced by TB‑infected macrophages and suppresses key anti‑bacterial cytokines (TNF‑α, IL‑6, IL‑1β, IL‑15).
- IL‑27 reduces the levels of the antimicrobial peptide LL‑37 and impairs autophagy‑related processes (LC3B lipidation, LAP pathway).
- Neutralizing IL‑27 and IL‑10 boosts proteins involved in bacterial clearance (vacuolar‑ATPase, NOX2, RUBCN) and restores LL‑37 production.
Practical Outcomes
- For biohackers, the work suggests that lowering IL‑27 activity or boosting LL‑37 could theoretically improve innate immunity against TB, but there are no safe, proven ways to do this in everyday life yet. At present, the findings are more of a mechanistic insight than a ready‑to‑use protocol.
Summary
The study shows that a signaling molecule called IL‑27, which is made when immune cells fight TB bacteria, actually dampens the cells' ability to kill the bacteria by lowering important defense proteins like the antimicrobial peptide LL‑37 and other cleanup mechanisms. Blocking IL‑27 (and also IL‑10) can restore these defenses and help the cells clear the infection better.
Abstract
Mycobacterium tuberculosis (M. tuberculosis) is an intracellular pathogen that primarily infects macrophages. Despite a robust anti-mycobacterial response, many times macrophages are unable to control M. tuberculosis. The purpose of this study was to investigate the mechanism by which the immunoregulatory cytokine IL-27 inhibits the anti-mycobacterial activity of primary human macrophages. We found concerted production of IL-27 and anti-mycobacterial cytokines by M. tuberculosis-infected macrophages in a toll-like receptor (TLR) dependent manner. Notably, IL-27 suppressed the production of anti-mycobacterial cytokines TNFα, IL-6, IL-1β, and IL-15 by M. tuberculosis-infected macrophages. IL-27 limits the anti-mycobacterial activity of macrophages by reducing Cyp27B, cathelicidin (LL-37), LC3B lipidation, and increasing IL-10 production. Furthermore, neutralizing both IL-27 and IL-10 increased the expression of proteins involved in LC3-associated phagocytosis (LAP) pathway for bacterial clearance, namely vacuolar-ATPase, NOX2, and RUN-domain containing protein RUBCN. These results implicate IL-27 is a prominent cytokine that impedes M. tuberculosis clearance.
Study Information
pubmed
2023
2023-02-24T00:00:00.000Z
10.1016/j.tube.2023.102326
7
74