In vivo-activated mononuclear phagocytes and protective immunity to chlamydiae in mice

Abstract

Peritoneal macrophages (Mφs) collected from Chlamydia psittaci 6BC-immune mice after intraperitoneal challenge with 106 6BC (immune-boosted [IB] Mφs) were compared by various functional criteria with other in vivo- and in vitro-activated Mφ populations. While casein-, protease peptone-, and thioglycolate (Thio)-elicited Mφs were equally susceptible to in vitro infection with 6BC, IB Mφs did not support chlamydial growth and Mφs from Mycobacterium tuberculosis BCG- or Listeria monocytogenes-sensitized mice exhibited intermediate susceptibility to infection. The resistance of IB Mφs was not due to the ingestion of fewer 6BC organisms, nor were these cells persistently infected, since chlamydiae could not be recovered from infected IB Mφs after in vitro infection, even after extended incubation times. In contrast, Thio Mφs stimulated in vitro with gamma interferon (IFN-γ), with or without lipopolysaccharide, resulted in cells that exhibited chlamydiastatic activity which was lost shortly after IFN-γ was removed from the culture medium. Conversely, the antichlamydial activity of IB Mφs was stable over time but not through the production of autostimulatory cytokines, as evidenced by the lack of stimulation of Thio Mφs to restrict 6BC replication in coculture experiments. IB Mφs exhibited enhanced oxidative activity, but anti-IFN-γ antibody did not abrogate this response. IB Mφs were recovered only from immunized mice that survived an otherwise lethal 6BC intraperitoneal challenge. These cells appear to be important for development of protective immunity to chlamydiae, and evidence suggests that stimulation by cytokines other than IFN-γ (with or without lipopolysaccharide) is required for the observed heightened in vivo activation.