Recombinant murine interferon-gamma reversibly activates rat alveolar macrophages to kill Legionella pneumophila.
The interaction of interferon (IFN)-gamma, rat alveolar macrophages, and Legionella pneumophila was studied in vitro to define the effector cell potential of alveolar macrophages against an intracellular pathogen in a model in which the efficacy of IFN-gamma could be tested in vivo. Alveolar macrophages preincubated with IFN-gamma up-regulated Ia antigen and killed 0.5-4 logs of L. pneumophila over 4 days compared with 1-2 logs of bacterial growth in untreated cells. The bactericidal effect was dose dependent, evident over a wide range of bacterial inocula, and not suppressed by hydrocortisone. Preincubation with IFN-gamma was unnecessary and insufficient, as intracellular replication was reversed by exposure to IFN-gamma up to 48 h after infection, and neutralization of IFN-gamma after infection permitted bacterial growth. IFN-gamma thus converts alveolar macrophages from target cells to effector cells in host defense against L. pneumophila and may be of therapeutic benefit in legionellosis.
Skerrett
S J
SJ
Medical Research Service, VA Medical Center, Seattle, WA 98108.
Martin
T R
TR
D000818:Animals; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007371:Interferon-gamma / Q000276:immunology*; D016952:Legionella pneumophila / Q000276:immunology*; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D007371:Interferon-gamma