Omega-3 polyunsaturated fatty acids impair in vivo interferon- gamma responsiveness via diminished receptor signaling.

BACKGROUND A high intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in mice causes impaired host resistance to Listeria monocytogenes. We wished to determine the role of interferon (IFN)-gamma signaling in this increased disease susceptibility. METHODS A feeding trial was conducted with mice unable to produce IFN-gamma (IFN-gamma KO); we provided exogenous recombinant IFN-gamma during L. monocytogenes challenge. The experimental diets were nutritionally complete and differed only in fat source: lard (devoid of n-3 PUFAs) or menhaden fish oil (rich in n-3 PUFAs). RESULTS The administration of IFN-gamma significantly enhanced bacterial clearance in IFN-gamma KO mice fed a diet devoid of n-3 PUFAs but had no effect in mice fed a diet rich in n-3 PUFAs. Ex vivo analysis of immune cells showed that n-3 PUFAs did not affect IFN-gamma receptor expression on immune cells. However, on IFN-gamma treatment, the phosphorylation of signal transducer and activator of transcription 1 was significantly reduced in peritoneal macrophages isolated from mice fed n-3 PUFAs. CONCLUSIONS These data suggest that diminished IFN-gamma signaling in murine macrophages is one mechanism by which n-3 PUFAs impair host resistance to L. monocytogenes. To our knowledge, this is the first report of a nutrient affecting IFN-gamma signaling and in vivo responsiveness to this cytokine.