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.
Irons
Robert
R
Department of Nutritional Sciences, University of Missouri, Columbia, Missouri, USA.
Fritsche
Kevin L
KL
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008088:Listeriosis / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010766:Phosphorylation; D017471:Receptors, Interferon / Q000378:metabolism*; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D000096743:Interferon gamma Receptor
D004268:DNA-Binding Proteins; D015525:Fatty Acids, Omega-3; D007371:Interferon-gamma; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494080:Stat1 protein, mouse