title: Differential responses to challenge with live and dead Mycobacterium bovis Bacillus Calmette-Guérin.
abstract: Bacillus Calmette-Guérin (BCG) vaccination has been shown to protect against challenge with virulent Mycobacterium tuberculosis in a range of experimental animal models: in each case, protective efficacy requires vaccination with live bacteria. With the goal of moving to a new generation of safer, nonliving vaccines, efforts have been made to identify the factors that determine the efficacy of live vaccination. We show that injection of live, but not dead, BCG induces localized swelling in the mouse footpad model. Live and dead bacteria induce similar responses during the first week after vaccination as determined by immunohistochemical analysis of the site of injection and of the draining lymph node. The subsequent differential response is characterized by migration of acid-fast bacilli to the draining lymph node in the case of the live vaccine. This is accompanied by an increase in mononuclear cells in the lymph node and by expression of inducible nitric oxide synthase (iNOS) both in the lymph node and at the site of injection. The ability of the bacteria to migrate to the lymph node may be an important element in the efficacy of live BCG vaccination.
authors.affiliation: Department of Medical Microbiology, Imperial College School of Medicine at St. Mary's, London, United Kingdom.
authors.forename: M A
authors.initials: MA
authors.lastname: Chambers
authors.forename: B G
authors.initials: BG
authors.lastname: Marshall
authors.forename: A
authors.initials: A
authors.lastname: Wangoo
authors.forename: A
authors.initials: A
authors.lastname: Bune
authors.forename: H T
authors.initials: HT
authors.lastname: Cook
authors.forename: R J
authors.initials: RJ
authors.lastname: Shaw
authors.forename: D B
authors.initials: DB
authors.lastname: Young
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000382:microbiology; D005260:Female; D005528:Foot; D006614:Hindlimb; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000737:chemistry / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D013194:Staining and Labeling; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology*
chemical_list: D001500:BCG Vaccine; D007375:Interleukin-1; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase