IL-26 contributes to host defense against intracellular bacteria
Angeline Tilly Dang, … , Barry R. Bloom, Robert L. Modlin
Angeline Tilly Dang, … , Barry R. Bloom, Robert L. Modlin
Published April 2, 2019
Citation Information: J Clin Invest. 2019;129(5):1926-1939. https://doi.org/10.1172/JCI99550.
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Research Article Immunology Infectious disease

IL-26 contributes to host defense against intracellular bacteria

Abstract

IL-26 is an antimicrobial protein secreted by Th17 cells that has the ability to directly kill extracellular bacteria. To ascertain whether IL-26 contributes to host defense against intracellular bacteria, we studied leprosy, caused by the obligate intracellular pathogen Mycobacterium leprae, as a model. Analysis of leprosy skin lesions by gene expression profiling and immunohistology revealed that IL-26 was more strongly expressed in lesions from the self-limited tuberculoid compared with expression in progressive lepromatous patients. IL-26 directly bound to M. leprae in axenic culture and reduced bacteria viability. Furthermore, IL-26, when added to human monocyte–derived macrophages infected with M. leprae, entered the infected cell, colocalized with the bacterium, and reduced bacteria viability. In addition, IL-26 induced autophagy via the cytoplasmic DNA receptor stimulator of IFN genes (STING), as well as fusion of phagosomes containing bacilli with lysosomal compartments. Altogether, our data suggest that the Th17 cytokine IL-26 contributes to host defense against intracellular bacteria.

Authors

Angeline Tilly Dang, Rosane M.B. Teles, David I. Weiss, Kislay Parvatiyar, Euzenir N. Sarno, Maria T. Ochoa, Genhong Cheng, Michel Gilliet, Barry R. Bloom, Robert L. Modlin

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Figure 2

IL-26 colocalization with CD4 and CD8.

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IL-26 colocalization with CD4 and CD8. (A) Immunofluorescence of IL-26 (...
(A) Immunofluorescence of IL-26 (green), CD4 (red), and nuclei (DAPI, blue) in T-lep and L-lep lesions. Data are representative of 4 individual samples. Original magnification, ×20. Scale bars: 10 μm (enlarged insets). (B) Colocalization of CD4 and IL-26, as determined by ImageJ. Data represent the mean ± SEM (n = 4). **P < 0.01, by 2-tailed Student’s t test. (C) Immunofluorescence of IL-26 (green), CD8 (red), and nuclei (DAPI, blue) in T-lep and L-lep lesions. White arrows indicate colocalization of green and red (yielding yellow). Original magnification, ×20. Scale bars: 10 μm (enlarged insets). (D) Colocalization of CD8 and IL-26, as determined by ImageJ. Data represent the mean ± SEM (n = 4). *P < 0.05, by 2-tailed Student’s t test. (E) Comparison of CD4 or CD8 colocalization with IL-26 in T-lep using ImageJ. Data represent the mean ± SEM (n = 4). *P < 0.05, by 2-tailed Student’s t test.