Interleukin-26 activates macrophages and facilitates killing of Mycobacterium tuberculosis

Abstract

Tuberculosis-causing Mycobacterium tuberculosis (Mtb) is transmitted via airborne droplets followed by a primary infection of macrophages and dendritic cells. During the activation of host defence mechanisms also neutrophils and T helper 1 (TH1) and TH17 cells are recruited to the site of infection. The TH17 cell-derived interleukin (IL)-17 in turn induces the cathelicidin LL37 which shows direct antimycobacterial effects. Here, we investigated the role of IL-26, a TH1- and TH17-associated cytokine that exhibits antimicrobial activity. We found that both IL-26 mRNA and protein are strongly increased in tuberculous lymph nodes. Furthermore, IL-26 is able to directly kill Mtb and decrease the infection rate in macrophages. Binding of IL-26 to lipoarabinomannan might be one important mechanism in extracellular killing of Mtb. Macrophages and dendritic cells respond to IL-26 with secretion of tumor necrosis factor (TNF)-α and chemokines such as CCL20, CXCL2 and CXCL8. In dendritic cells but not in macrophages cytokine induction by IL-26 is partly mediated via Toll like receptor (TLR) 2. Taken together, IL-26 strengthens the defense against Mtb in two ways: firstly, directly due to its antimycobacterial properties and secondly indirectly by activating innate immune mechanisms.

The Kinocidin Interleukin-26 Shows Immediate Antimicrobial Effects Even to Multi-resistant Isolates

“…In a third publication, an activity against biofilm formation of S. aureus was detected which was more pronounced for IL-26 than for the AMP LL-37 (Woetmann et al, 2018). Regarding Mycobacteria (M.) IL-26 has been shown to inhibit growth and reduce viability of M. leprae and M. tuberculosis in axenic cultures as well as within macrophages, probably by inducing lysis by bleb-formation after interaction with lipoarabinomannan (Dang et al, 2019;Hawerkamp et al, 2020). The reason for these functional differences might be due to the different sources and qualities of commercially available IL-26 (Knappe et al, 2000;Hör et al, 2004).…”

Interleukin-26 Expression in Inflammatory Bowel Disease and Its Immunoregulatory Effects on Macrophages

“…Unraveling the immunoregulatory effects of IL-26 on macrophages may provide critical insights into the roles of IL-26 in IBD. IL-26 has been reported to polarize macrophages into the M1 phenotype and enhance the expression of CCL20, CXCL8, and CXCL2 mRNA as well as the secretion of TNF-α in THP-1 macrophages ( 23 , 24 ). However, to date, a comprehensive transcriptomic analysis of IL-26-exposed macrophages has not been previously reported.…”

A comprehensive review of IL‐26 to pave a new way for a profound understanding of the pathobiology of cancer, inflammatory diseases and infections

“…In terms of protein level, IL-26 was higher in noninfected monocytes, which was diminished after infection with tuberculosis. Also, IL-26 levels were somehow higher in non-tuberculous than tuberculous in younger adults but not in elders [62]. According to these results, due to the inhibition of IL-26 production in infected cells, it was assumed that IL-26 exerts significant inhibitory effects on tuberculosis [63].…”

“…One inhibitory effect of IL-26 on tuberculosis is attributed to IL-26's unique structure. It has been shown that IL-26 can bind to lipoarabinomannan on the bacterial surface [62]. This capability of IL-26 possibly acts like LL-37 (an antibacterial peptide) and induces pore formation.…”

“…Another underlying mechanism proposed for the anti-tuberculosis function of IL-26 relies on the activation of macrophages and inducing inflammation. It is suggested that IL-26 induces TLR2 signalling to induce TNF-α, CXCL2 and CXCL8 and enhances the killing activity of macrophages [62].…”