title: Novel role for IL-22 in protection during chronic Mycobacterium tuberculosis HN878 infection.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri, USA.
authors.forename: P
authors.initials: P
authors.lastname: Treerat
authors.affiliation: Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri, USA.
authors.forename: O
authors.initials: O
authors.lastname: Prince
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", Mexico City, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Cruz-Lagunas
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", Mexico City, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Muñoz-Torrico
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", Mexico City, Mexico.
authors.forename: M A
authors.initials: MA
authors.lastname: Salazar-Lezama
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", Mexico City, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Selman
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: B
authors.initials: B
authors.lastname: Fallert-Junecko
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Reinhardt
authors.affiliation: Division of Pulmonology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Alcorn
authors.affiliation: Divisions of Bacteriology and Parasitology, Tulane National Primate Research Centre, Covington, Louisiana, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kaushal
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", Mexico City, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Zuñiga
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Centre, Rochester, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rangel-Moreno
authors.affiliation: Richard King Mellon Institute for Pediatric Research, Department of Pediatrics and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Kolls
authors.affiliation: Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Khader
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D004351:Drug Resistance; D004847:Epithelial Cells / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D051195:Toll-Like Receptor 2; D000097043:Interleukin-22; C493486:Tlr2 protein, mouse