Novel role for IL-22 in protection during chronic Mycobacterium tuberculosis HN878 infection

• Published in: Mucosal immunology Vol. 10; no. 4; pp. 1069 - 1081
• Main Authors: Treerat, P, Prince, O, Cruz-Lagunas, A, Muñoz-Torrico, M, Salazar-Lezama, M A, Selman, M, Fallert-Junecko, B, Reinhardt, T A, Alcorn, J F, Kaushal, D, Zuñiga, J, Rangel-Moreno, J, Kolls, J K, Khader, S A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2017; Elsevier Limited
• Subjects: 631/250/347; 631/250/516; 631/45/127/1213; 692/699/255/1856; Allergology; Animal models; Animals; Antibodies; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Chronic Disease; Chronic infection; Clinical isolates; Disease resistance; Drug Resistance; Epithelial cells; Epithelial Cells - immunology; Gastroenterology; Humans; Immunity, Mucosal; Immunology; Infections; Interleukin 10; Interleukin 22; Interleukins - genetics; Interleukins - metabolism; Lung - immunology; Lung - microbiology; Lung - pathology; Macaca mulatta; Macrophages; Macrophages - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucosa; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Rodents; TLR2 protein; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Toll-like receptors; Tuberculosis; Tuberculosis - immunology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2017.15

Approximately 2 billion people are infected with Mycobacterium tuberculosis ( Mtb ), resulting in 1.4 million deaths every year. Among Mtb -infected individuals, clinical isolates belonging to the W-Beijing lineage are increasingly prevalent, associated with drug resistance, and cause severe disease immunopathology in animal models. Therefore, it is exceedingly important to identify the immune mechanisms that mediate protection against rapidly emerging Mtb strains, such as W-Beijing lineage. IL-22 is a member of the IL-10 family of cytokines with both protective and pathological functions at mucosal surfaces. Thus far, collective data show that IL-22 deficient mice are not more susceptible to aerosolized infection with less virulent Mtb strains. Thus, in this study we addressed the functional role for the IL-22 pathway in immunity to emerging Mtb isolates, using W-Beijing lineage member, Mtb HN878 as a prototype. We show that Mtb HN878 stimulates IL-22 production in TLR2 dependent manner and IL-22 mediates protective immunity during chronic stages of Mtb HN878 infection in mice. Interestingly, IL-22-dependent pathways in both epithelial cells and macrophages mediate protective mechanisms for Mtb HN878 control. Thus, our results project a new protective role for IL-22 in emerging Mtb infections.