Robert Irons

Omega-3 Polyunsaturated Fatty Acids Impair In Vivo Interferon-γ 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.

n −3 PUFA fail to affect in vivo , antigen-driven CD8 + T-cell proliferation in the spleen of naïve mice

One of the most frequently reported immunomodulatory actions of n-3 PUFA is their ability to diminish in vitro lymphocyte proliferation. The purpose of this study was to determine if n-3 PUFA intake affects the kinetics or magnitude of the antigen-driven expansion of CD8(+)T-lymphocytes in vivo. In this study we utilized a well-characterized model of T-cell immunity (i.e. infection with the intracellular bacterium, Listeria monocytogenes). Weanling BALB/c mice were fed one of two experimental diets that differed solely in fat source. Our control diet contained lard (180 g/kg) and was devoid of long-chain n-3 PUFA. The experimental diet contained 150 g/kg menhaden fish oil and 30 g/kg corn oil, thus providing approximately 8 % of energy from long-chain n-3 PUFA. After 4 weeks, mice were infected intravenously with 10(6) colony-forming units of actA-deficient L. monocytogenes. Clonal expansion of antigen-specific CD8(+)T-cells in the spleen was measured at 5, 7, 9 and 14 d post-challenge using a class I MHC tetramer loaded with the immunodominant peptide from this pathogen (i.e. K(d):LLO91-99). We report that feeding mice a diet rich in n-3 fatty acids did not significantly impact either the kinetics or magnitude of in vivo, antigen-driven expansion of CD8(+)T-cells. Furthermore, contraction of this T-cell population was not affected by n-3 PUFA treatment. To our knowledge this is the first time MHC tetramers have been used to investigate the influence of n-3 PUFA on in vivo CD8(+)T-cell proliferation.