Docosahexaenoic acid improves the decrement in antibody production upon influenza infection in murine obesity through the production of pro-resolving lipid mediators

Abstract

Abstract Obesity is associated with diminished antibody production against influenza infection. Therefore, therapeutic strategies are needed to enhance humoral immunity. We previously demonstrated that essential long-chain n-3 polyunsaturated fatty acids (PUFA) enhance humoral responses to a T-independent antigen. Thus, here we hypothesized that the n-3 PUFA docosahexaenoic acid (DHA) could improve antibody production upon influenza infection in obese mice. To test the hypothesis, mice were fed for 15 weeks with a control or a Western diet with or without DHA supplementation followed by infection with influenza A/Puerto Rico/8/34. The data show that DHA supplementation improved antibody titers, as measured by HAI and microneutralization assays, in obese mice after influenza infection. Mechanistically, DHA did not target B-cell PPARγ or the DHA-sensing G-protein coupled receptor 120 to boost antibody levels. Instead, DHA increased the levels of downstream D-series specialized pro-resolving lipid mediators (SPMs), which are known to increase antibody production through the generation of CD138+ antibody secreting cells. Specifically, LC/MS analyses showed 14-HDHA to be elevated upon DHA intervention, which elevated antibody levels upon infection and increased the frequency of CD138+ cells. Overall, the results suggest that DHA may have potential therapeutic applications for improving humoral immunity, potentially through an SPM mediated mechanism.