title: Inflammation and lymphocyte activation during mycobacterial infection in the interferon-gamma-deficient mouse.
abstract: Interferon-gamma is a pivotal cytokine in the protective response to tuberculosis. In its absence rampant bacterial growth results in tissue destruction and death. While macrophage activation is key, this pleiotropic cytokine has other secondary but significant roles. To investigate these roles, both intravenous and aerosol infection of the IFN-gamma gene disrupted (GKO) mouse was performed. For the first time we describe the very similar growth of bacteria, during the initial phase of infection, between control and GKO mice. During this initial phase, however, very different histopathologic consequences between control and GKO mice were observed. Key observations included an early increased accumulation of granulocytes and a much more rapid and pronounced interstitial pneumonia in the GKO mice. As infection developed, GKO mice mounted an antigen-specific response; however, lymphocyte activation was much more rapid in these mice. Of interest is the fact that this increased rapidity occurred prior to significant differences in bacterial number. Taken together these data support a role for IFN-gamma in limiting both initial cellular recruitment and acquired lymphocytic responses to mycobacterial infection. This role may be key in surviving the kind of chronic stimulatory disease caused by Mycobacterium tuberculosis.
authors.affiliation: Mycobacterial Research Laboratories, Colorado State University, Fort Collins, Colorado 80523, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Pearl
authors.forename: B
authors.initials: B
authors.lastname: Saunders
authors.forename: S
authors.initials: S
authors.lastname: Ehlers
authors.forename: I M
authors.initials: IM
authors.lastname: Orme
authors.forename: A M
authors.initials: AM
authors.lastname: Cooper
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015169:Colony Count, Microbial; D004198:Disease Susceptibility; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics* / Q000502:physiology*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D014373:Tuberculin / Q000494:pharmacology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D014373:Tuberculin; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse