title: Infection biology of a novel alpha-crystallin of Mycobacterium tuberculosis: Acr2.
abstract: Heat shock proteins assist the survival of Mycobacterium tuberculosis (MTB) but also provide a signal to the immune response. The gene most strongly induced by heat shock in MTB is Rv0251c, which encodes Acr2, a novel member of the alpha-crystallin family of molecular chaperones. The expression of acr2 increased within 1 h after infection of monocytes or macrophages, reaching a peak of 18- to 55-fold by 24 h. Inhibition of superoxide action reduced the intracellular increase in acr2. Despite this contribution to the stress response of MTB, the gene for acr2 appears dispensable; a deletion mutant (Deltaacr2) was unimpaired in log phase growth and persisted in IFN-gamma-activated human macrophages. Acr2 protein was strongly recognized by cattle with early primary Mycobacterium bovis infection and by healthy MTB-sensitized people. Within the latter group, those with recent exposure to infectious tuberculosis had, on average, 2.6 times the frequency of Acr2-specific IFN-gamma-secreting T cells than those with more remote exposure (p = 0.009). These data show that, by its up-regulation early after entry to cells, Acr2 gives away the presence of MTB to the immune response. The demonstration that there is infection stage-specific immunity to tuberculosis has implications for vaccine design.
authors.affiliation: Wellcome Trust Center for Research in Clinical Tropical Medicine and Department of Pediatric Infectious Diseases, Faculty of Medicine, Imperial College London, Wright Fleming Institute, UK.
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Graham R
authors.initials: GR
authors.lastname: Stewart
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Newton
authors.forename: H Martin
authors.initials: HM
authors.lastname: Vordermeier
authors.forename: John R
authors.initials: JR
authors.lastname: Wain
authors.forename: Helen N
authors.initials: HN
authors.lastname: Murphy
authors.forename: Katherine
authors.initials: K
authors.lastname: Horner
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Young
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000818:Animals; D002417:Cattle; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D009000:Monocytes / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000276:immunology / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014376:Tuberculosis / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000276:immunology; D015854:Up-Regulation; D038201:alpha-Crystallins / Q000235:genetics* / Q000276:immunology* / Q000502:physiology
chemical_list: D038201:alpha-Crystallins; C500452:alpha-crystallin 2, Mycobacterium tuberculosis