title: A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion.
abstract: Six major lineages of Mycobacterium tuberculosis appear preferentially transmitted amongst distinct ethnic groups. We identified a deletion affecting Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that coincidentally defines the East African-Indian lineage matching a major ethnic group in this city. In broth media, CH grew less rapidly and was less acidic and H2O2-tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless, CH was not impaired in its ability to grow in human monocyte-derived macrophages. When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and more antiinflammatory IL-10 and IL-6 gene transcription and secretion from monocyte-derived macrophages. It thus appears that CH compensates microbiological attenuation by skewing the innate response toward phagocyte deactivation. Complementation of Rv1519, but none of nine additional genes absent from CH compared with the type strain, H37Rv, reversed the capacity of CH to elicit antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M. tuberculosis confers an immune subverting phenotype that contributes to the persistence and outbreak potential of this lineage.
authors.affiliation: Wellcome Trust Center for Research in Clinical Tropical Medicine, Center for Molecular Microbiology and Infection, and Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College London, London W2 1PG, United Kingdom.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Newton
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Mark P
authors.initials: MP
authors.lastname: Nicol
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Garton
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Staples
authors.forename: Graham R
authors.initials: GR
authors.lastname: Stewart
authors.forename: John R
authors.initials: JR
authors.lastname: Wain
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Martineau
authors.forename: Sarah
authors.initials: S
authors.lastname: Fandrich
authors.forename: Timothy
authors.initials: T
authors.lastname: Smallie
authors.forename: Brian
authors.initials: B
authors.lastname: Foxwell
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Obaidi
authors.forename: Jamila
authors.initials: J
authors.lastname: Shafi
authors.forename: Kumar
authors.initials: K
authors.lastname: Rajakumar
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.forename: Loems
authors.initials: L
authors.lastname: Ziegler-Heitbrock
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D001208:Asia; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D018562:Disease Transmission, Infectious; D005006:Ethnicity; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D010586:Phagocytes / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D010641:Phenotype; D011110:Polymorphism, Genetic; D014376:Tuberculosis / Q000453:epidemiology / Q000276:immunology / Q000635:transmission; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines