Interleukin-26 activates macrophages and facilitates killing of Mycobacterium tuberculosis

Heike C. Hawerkamp; Lasse van Geelen; Jan Korte; Jeremy Di Domizio; Marc Swidergall; Afaque Ahmad Imtiyaz Momin; Francisco J. Guzmán-Vega; Stefan T. Arold; Joachim Ernst; Michel Gilliet; Rainer Kalscheuer; Bernhard Homey; Stephan Meller

doi:10.1038/s41598-020-73989-y

Interleukin-26 activates macrophages and facilitates killing of Mycobacterium tuberculosis

Heike C. Hawerkamp, Lasse van Geelen, Jan Korte, Jeremy Di Domizio, Marc Swidergall, Afaque Ahmad Imtiyaz Momin, Francisco J. Guzmán-Vega, Stefan T. Arold, Joachim Ernst, Michel Gilliet, Rainer Kalscheuer, Bernhard Homey, Stephan Meller

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Abstract

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.

Original language	English (US)
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-73989-y
State	Published - Oct 14 2020

Bibliographical note

KAUST Repository Item: Exported on 2020-10-16
Acknowledgements: We thank S. Köhler from the Center for Advanced Imaging, Heinrich-Heine-University Düsseldorf for performing SEM. We further thank H. Mayringer, N. Simiantonaki and I. Esposito from the Institute of Pathology, Medical Faculty, Heinrich-Heine-University Düsseldorf for providing FFPE-lymph node sections from healthy individuals and tuberculosis patients. S. Meller was supported by the Stettendorf Stiftung.

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@article{89a29873a145467d8449bafc1a100418,

title = "Interleukin-26 activates macrophages and facilitates killing of Mycobacterium tuberculosis",

abstract = "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.",

author = "Hawerkamp, {Heike C.} and {van Geelen}, Lasse and Jan Korte and {Di Domizio}, Jeremy and Marc Swidergall and Momin, {Afaque Ahmad Imtiyaz} and Guzm{\'a}n-Vega, {Francisco J.} and Arold, {Stefan T.} and Joachim Ernst and Michel Gilliet and Rainer Kalscheuer and Bernhard Homey and Stephan Meller",

note = "KAUST Repository Item: Exported on 2020-10-16 Acknowledgements: We thank S. K{\"o}hler from the Center for Advanced Imaging, Heinrich-Heine-University D{\"u}sseldorf for performing SEM. We further thank H. Mayringer, N. Simiantonaki and I. Esposito from the Institute of Pathology, Medical Faculty, Heinrich-Heine-University D{\"u}sseldorf for providing FFPE-lymph node sections from healthy individuals and tuberculosis patients. S. Meller was supported by the Stettendorf Stiftung.",

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day = "14",

doi = "10.1038/s41598-020-73989-y",

language = "English (US)",

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journal = "Scientific Reports",

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T1 - Interleukin-26 activates macrophages and facilitates killing of Mycobacterium tuberculosis

AU - Hawerkamp, Heike C.

AU - van Geelen, Lasse

AU - Korte, Jan

AU - Di Domizio, Jeremy

AU - Swidergall, Marc

AU - Momin, Afaque Ahmad Imtiyaz

AU - Guzmán-Vega, Francisco J.

AU - Arold, Stefan T.

AU - Ernst, Joachim

AU - Gilliet, Michel

AU - Kalscheuer, Rainer

AU - Homey, Bernhard

AU - Meller, Stephan

N1 - KAUST Repository Item: Exported on 2020-10-16 Acknowledgements: We thank S. Köhler from the Center for Advanced Imaging, Heinrich-Heine-University Düsseldorf for performing SEM. We further thank H. Mayringer, N. Simiantonaki and I. Esposito from the Institute of Pathology, Medical Faculty, Heinrich-Heine-University Düsseldorf for providing FFPE-lymph node sections from healthy individuals and tuberculosis patients. S. Meller was supported by the Stettendorf Stiftung.

PY - 2020/10/14

Y1 - 2020/10/14

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/665596

UR - http://www.nature.com/articles/s41598-020-73989-y

U2 - 10.1038/s41598-020-73989-y

DO - 10.1038/s41598-020-73989-y

M3 - Article

C2 - 33057074

SN - 2045-2322

VL - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

ER -

Interleukin-26 activates macrophages and facilitates killing of Mycobacterium tuberculosis

Abstract

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