title: Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils.
abstract: Neutrophils enter sites of infection, where they can eliminate pathogenic bacteria in an oxidative manner. Despite their predominance in active tuberculosis lesions, the function of neutrophils in this important human infection is still highly controversial. We observed that virulent Mycobacterium tuberculosis survived inside human neutrophils despite prompt activation of these defence cells' microbicidal effectors. Survival of M. tuberculosis was accompanied by necrotic cell death of infected neutrophils. Necrotic cell death entirely depended on radical oxygen species production since chronic granulomatous disease neutrophils were protected from M. tuberculosis-triggered necrosis. More, importantly, the M. tuberculosis ΔRD1 mutant failed to induce neutrophil necrosis rendering this strain susceptible to radical oxygen species-mediated killing. We conclude that this virulence function is instrumental for M. tuberculosis to escape killing by neutrophils and contributes to pathogenesis in tuberculosis.
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, WC1E 7HT, London, UK.
authors.forename: Björn
authors.initials: B
authors.lastname: Corleis
authors.forename: Daniel
authors.initials: D
authors.lastname: Korbel
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
authors.forename: Johan
authors.initials: J
authors.lastname: Bylund
authors.forename: Ronnie
authors.initials: R
authors.lastname: Chee
authors.forename: Ulrich E
authors.initials: UE
authors.lastname: Schaible
mesh_terms: D000293:Adolescent; D000328:Adult; D016923:Cell Death; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity*; D014774:Virulence; D055815:Young Adult
chemical_list: D017382:Reactive Oxygen Species