Interferon-gamma mediated immune effector mechanisms against Bordetella pertussis

The role of IFN-gamma in reducing the intracellular load of Bordetella pert ussis in murine macrophages in vitro has been examined. The results demonst rate that exposure to IFN-gamma can reduce bacterial load in viable macroph ages and that this is associated with production of nitric oxide (NO). Thes e observations provide a mechanism by which IFN-gamma may mediate its antim icrobial effect and support an important role for activated alveolar macrop hages 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 restrict ion may be an important mechanism by which IFN-gamma influences bacterial s urvival within mouse macrophages. It is also shown that IFN-gamma may media te its effect through NO independent mechanisms and that B. pertussis is se nsitive to agents that stimulate the respiratory burst. Finally, it is show n that the concentration of L-tryptophan may be a limiting step in the intr acellular survival of B. pertussis and that the induction of tryptophan deg rading enzymes may be an additional mechanism through which IFN-gamma exert s its antimicrobial effects against B. pertussis. (C) 1999 Elsevier Science B.V. All rights reserved.