Interferon-γ mediated immune effector mechanisms against Bordetella pertussis

The role of IFN-gamma in reducing the intracellular load of Bordetella pertussis in murine macrophages in vitro has been examined. The results demonstrate that exposure to IFN-gamma can reduce bacterial load in viable macrophages and that this is associated with production of nitric oxide (NO). These observations provide a mechanism by which IFN-gamma may mediate its antimicrobial effect and support an important role for activated alveolar macrophages in the elimination of B. pertussis from the respiratory tract. Using intracellular iron chelation, it is shown that intracellular survival of B. pertussis is dependant on iron availability and suggest that iron restriction may be an important mechanism by which IFN-gamma influences bacterial survival within mouse macrophages. It is also shown that IFN-gamma may mediate its effect through NO independent mechanisms and that B. pertussis is sensitive to agents that stimulate the respiratory burst. Finally, it is shown that the concentration of L-tryptophan may be a limiting step in the intracellular survival of B. pertussis and that the induction of tryptophan degrading enzymes may be an additional mechanism through which IFN-gamma exerts its antimicrobial effects against B. pertussis. (C) 1999 Elsevier Science B.V. All rights reserved.