Interleukin-26 Differentially Modulates Human Macrophage Inflammatory Response to Distinct Mycobacterium tuberculosis Whole Cell Lysates

Abstract

Background: Interleukin-26 (IL-26) is an antimicrobial peptide that may contribute to the elimination of intracellular Mycobacterium tuberculosis (Mtb). The aim of the study was to investigate how IL-26 affected the response of human macrophages to Mtb whole cell lysates from different lineages.

Methods: Human macrophages were treated with IL-26 (monomer or dimer) before stimulation with Mtb lysates from Indo-Oceanic, HN878, East-African-Indian, and CDC1551 strains.

Results: Nuclear factor kappa B (NF-κB) activation was similar in untreated cells after stimulation with all lysates, but was diminished in IL-26 monomer-treated macrophages in response to Indo-Oceanic lysates. Macrophage exposure to dimeric IL-26 led to a higher NF-κB activation in response to CDC1551 lysates, but lower to HN878 lysates. No changes were observed in interferon regulatory factor (IRF) activation. Overall, IL-26 modulates NF-κB activation in a strain and confirmation-dependent manner. This modulation influences the macrophage inflammatory response to Mtb. Our results suggest that IL-26 may promote M1 polarization and enhance anti-Mtb immunity through the NF-κB pathway. This is particularly true in response to high-cytokine-inducing strains like CDC1551.

Conclusion: More studies are needed to clarify IL-26’s dual role in inflammation and immune regulation, and to explore its therapeutic potential in tuberculosis (TB) treatment and vaccine strategies.