Differential Induction of Gamma Interferon in Legionella pneumophila - Infected Macrophages from BALB/c and A/J Mice

Abstract

ABSTRACT Gamma interferon (IFN-γ), a pleiotropic cytokine, is now known to be produced by macrophages as well as by NK cells, γδ cells, and activated T cells. The autocrine biological functions of IFN-γ 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-γ 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-γ mRNA at 24 and 28 h, which corresponded to the initiation of anti- L. pneumophila activity. Moreover, IFN-γneutralization by antibody treatment of the cultures resulted in increased L. pneumophila growth in the macrophages. In contrast, no IFN-γ mRNA was expressed in TG-macrophages from A/J mice, where L. pneumophila grew unrestricted. As would be expected, IFN-γ treatment decreased bacterial growth. An IFN-γ-mediated antibacterial activity was, however, inducible in A/J macrophages by the addition of interleukin-12 following L. pneumophila infection. Thus, autocrine IFN-γ is involved in anti- L. pneumophila activity associated with different growth patterns and appears to be important during intracellular infection.