Dietary polyunsaturated fatty acids modulate immunity to influenza virus infection

Dietary fish oils, rich in n-3 polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to have anti-inflammatory properties. While the immunosuppressive effects of n-3 PUFA may be beneficial for some chronic inflammatory disorders, these same anti-inflammatory properties may be detrimental for a response to an infection when a functional immune system is needed to eradicate an invading pathogen.;Despite the availability of vaccines and antiviral agents, influenza virus continues to be a major cause of morbidity and mortality worldwide. Given that n-3 PUFA-rich fish oil supplementation by human populations is on the rise, and with the increasing threat of an influenza pandemic, we tested the impact of fish oil feeding on the immune response to influenza virus infection.;Using in vivo and in vitro models, we found n-3 PUFA, supplied at physiologically relevant levels, suppressed immune responses following influenza infection. Although the anti-inflammatory properties of fish oil resulted in decreased lung inflammation in influenza infected mice, it also led to increased mortality and increased viral titers in surviving mice post infection. Impairment of host resistance was likely due to reduced inflammatory cell trafficking into the lungs in conjunction with lower cytokine production during infection. Influenza virus infection also resulted in a significant increase in EPA content in the infected lung, while infection had little effect on DHA in fish oil fed mice. Although changes in fatty acid membrane profiles can result in functional changes, dendritic cells and T cells from infected fish oil fed mice were able to respond to viral antigen equivalent to control fed mice.;In response to viral infection, airway epithelial cells induce pro-inflammatory and antiviral mediators. We found that specific DHA to EPA ratios suppressed these mediators of infected human primary bronchial epithelial cells. Together, data from our studies indicate that n-3 PUFA treatment can have a profound effect in the host response to influenza virus infection.;Given that fish oil supplementation is used by both adults and children, there is a significant public health benefit in further investigating how PUFAs alter immune function.