Infection biology of a novel alpha-crystallin of Mycobacterium tuberculosis: Acr2.
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.
Wilkinson
Katalin A
KA
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.
Stewart
Graham R
GR
Newton
Sandra M
SM
Vordermeier
H Martin
HM
Wain
John R
JR
Murphy
Helen N
HN
Horner
Katherine
K
Young
Douglas B
DB
Wilkinson
Robert J
RJ
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
D038201:alpha-Crystallins; C500452:alpha-crystallin 2, Mycobacterium tuberculosis