title: Predominance of interleukin-22 over interleukin-17 at the site of disease in human tuberculosis.
abstract: The inflammatory response to Mycobacterium tuberculosis (M.tb) at the site of disease is Th1 driven. Whether the Th17 cytokines, IL-17 and IL-22, contribute to this response in humans is unknown. We hypothesized that IL-17 and IL-22 contribute to the inflammatory response in pleural and pericardial disease sites of human tuberculosis (TB). We studied pleural and pericardial effusions, established TB disease sites, from HIV-uninfected TB patients. Levels of soluble cytokines were measured by ELISA and MMP-9 by luminex. Bronchoalveolar lavage or pericardial mycobacteria-specific T cell cytokine expression was analyzed by intracellular cytokine staining. IL-17 was not abundant in pleural or pericardial fluid. IL-17 expression by mycobacteria-specific disease site T cells was not detected in healthy, M.tb-infected persons, or patients with TB pericarditis. These data do not support a major role for IL-17 at established TB disease sites in humans. IL-22 was readily detected in fluid from both disease sites. These IL-22 levels exceeded matching peripheral blood levels. Further, IL-22 levels in pericardial fluid correlated positively with MMP-9, an enzyme known to degrade the pulmonary extracellular matrix. We propose that our findings support a role for IL-22 in TB-induced pathology or the resulting repair process.
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa. kerryn.matthews@uct.ac.za
authors.forename: Kerryn
authors.initials: K
authors.lastname: Matthews
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Barbara
authors.initials: B
authors.lastname: Kalsdorf
authors.forename: Teri
authors.initials: T
authors.lastname: Roberts
authors.forename: Andreas
authors.initials: A
authors.lastname: Diacon
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.forename: Janine
authors.initials: J
authors.lastname: Wolske
authors.forename: Mpiko
authors.initials: M
authors.lastname: Ntsekhe
authors.forename: Faisal
authors.initials: F
authors.lastname: Syed
authors.forename: James
authors.initials: J
authors.lastname: Russell
authors.forename: Bongani M
authors.initials: BM
authors.lastname: Mayosi
authors.forename: Rodney
authors.initials: R
authors.lastname: Dawson
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D015496:CD4-Positive T-Lymphocytes; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010495:Pericarditis, Tuberculous / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D000942:Antigens, Bacterial; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22