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.
Highlights
Tuberculosis-causing Mycobacterium tuberculosis (Mtb) is transmitted via airborne droplets followed by a primary infection of macrophages and dendritic cells
We report here that both IL-26 gene and protein expression are significantly increased in tuberculosis and sarcoidosis
Similar surface lesions on Mtb are caused by granulysin, a protein released by cytolytic T cells during antimycobacterial responses[10]
Summary
Tuberculosis-causing Mycobacterium tuberculosis (Mtb) is transmitted via airborne droplets followed by a primary infection of macrophages and dendritic cells. Tuberculosis is transmitted via airborne droplets containing Mtb which initially infects, and mainly resides intracellularly in macrophages and in dendritic cells (DCs)[6]. Mycobacteria enter both cell types via phagocytosis. During granuloma formation in later stages Mtb may persist in m acrophages[8] Various endogenous agents such as granulysin, human beta-defensin 2 (hBD2)[9,10], and LL37 are able to kill Mtb in vitro[11,12,13]. Macrophages are able to uptake these NETs containing LL37 Within lysosomal compartments, these AMP-nucleic acid complexes display antimicrobial activity against m ycobacteria[17]. Several subtypes of T cells play central role during Mtb infection: Similar to NK cells, cytolytic T lymphocytes and γδ T cells release granulysin and perforin that lyse infected macrophages and Scientific Reports | (2020) 10:17178
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