Differential induction of gamma interferon in Legionella pneumophila-infected macrophages from BALB/c and A/J mice.
Gamma interferon (IFN-gamma), a pleiotropic cytokine, is now known to be produced by macrophages as well as by NK cells, gammadelta cells, and activated T cells. The autocrine biological functions of IFN-gamma on the macrophage include the upregulation of major histocompatibility complex MHC class II and the activation to an antiviral state. In this study, the production of IFN-gamma by macrophages was demonstrated to correspond to antibacterial activity. Legionella pneumophila replicates intracellularly in thioglycolate (TG)-elicited macrophages (TG-macrophages) from A/J mice, while TG-macrophages from BALB/c mice restrict bacterial growth after an initial period of growth. BALB/c TG-macrophages were shown to express IFN-gamma mRNA at 24 and 28 h, which corresponded to the initiation of anti-L. pneumophila activity. Moreover, IFN-gammaneutralization by antibody treatment of the cultures resulted in increased L. pneumophila growth in the macrophages. In contrast, no IFN-gamma mRNA was expressed in TG-macrophages from A/J mice, where L. pneumophila grew unrestricted. As would be expected, IFN-gamma treatment decreased bacterial growth. An IFN-gamma-mediated antibacterial activity was, however, inducible in A/J macrophages by the addition of interleukin-12 following L. pneumophila infection. Thus, autocrine IFN-gamma is involved in anti-L. pneumophila activity associated with different growth patterns and appears to be important during intracellular infection.
Salins
S
S
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612, USA.
Newton
C
C
Widen
R
R
Klein
T W
TW
Friedman
H
H
D000818:Animals; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000494:pharmacology; D016952:Legionella pneumophila / Q000254:growth & development* / Q000276:immunology; D007877:Legionnaires' Disease / Q000276:immunology / Q000382:microbiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D013864:Thioglycolates / Q000494:pharmacology
D012333:RNA, Messenger; D013864:Thioglycolates; D018664:Interleukin-12; D007371:Interferon-gamma