Interleukin-26 activates macrophages and facilitates killing of Mycobacterium tuberculosis

• Published in: Scientific reports Vol. 10; no. 1; p. 17178
• Main Authors: Hawerkamp, Heike C., van Geelen, Lasse, Korte, Jan, Di Domizio, Jeremy, Swidergall, Marc, Momin, Afaque A., Guzmán-Vega, Francisco J., Arold, Stefan T., Ernst, Joachim, Gilliet, Michel, Kalscheuer, Rainer, Homey, Bernhard, Meller, Stephan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-10-2020
• Subjects: 692/699/249/2510; 692/699/255/1856; Adult; Aged; Cell Line; Cytokines - immunology; Cytokines - metabolism; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; HEK293 Cells; Humanities and Social Sciences; Humans; Interleukins - immunology; Interleukins - metabolism; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Macrophages - immunology; Macrophages - metabolism; Male; Middle Aged; multidisciplinary; Mycobacterium tuberculosis - immunology; RNA, Messenger - immunology; RNA, Messenger - metabolism; Science; Science (multidisciplinary); THP-1 Cells - immunology; THP-1 Cells - metabolism; Tuberculosis - immunology; Tuberculosis - metabolism; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-73989-y

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 (T
H
1) and T
H
17 cells are recruited to the site of infection. The T
H
17 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 T
H
1- and T
H
17-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.