Omega‐3 Polyunsaturated Fatty Acids Impair In Vivo Interferon‐γ Responsiveness via Diminished Receptor Signaling
Departments of Nutritional Sciences, Animal Sciences, and Microbiology and Molecular Immunology, University of Missouri, Columbia
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)–γ signaling in this increased disease susceptibility.
Methods.A feeding trial was conducted with mice unable to produce IFN‐γ (IFN‐γKO); we provided exogenous recombinant IFN‐γ 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‐γ significantly enhanced bacterial clearance in IFN‐γKO 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‐γ receptor expression on immune cells. However, on IFN‐γ 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‐γ 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‐γ signaling and in vivo responsiveness to this cytokine.
Received 7 July 2004; accepted 31 August 2004; electronically published 28 December 2004.
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Presented in part: Experimental Biology meeting, San Diego, 11–15 April 2003 (abstract 698.4).
Financial support: US Department of Agriculture (grant 00‐35200‐9115); University of Missouri Food‐for‐the‐21st‐Century Program.