Docosahexaenoic Acid Supplementation Represses the Early Immune Response Against Murine Cytomegalovirus but Enhances NK Cell Effector Function

Abstract

Background Docosahexaenoic acid (DHA) supplementation is beneficial for several chronic diseases; however, its effect on immune regulation is still debated. Given the prevalence of cytomegalovirus (CMV) infection and because natural killer (NK) cells are the component of innate immunity critical for controlling CMV infection, the current study explored the effect of a DHA-enriched diet on susceptibility and the NK cell effector response to murine (M) CMV infection. Results Male C57BL/6 mice fed a control or DHA-enriched diet for 3 weeks were infected with MCMV and sacrificed at the indicated time points postinfection. Compared with control mice, DHA-fed mice had higher liver and spleen viral loads on day 7 postinfection, but final MCMV clearance was not affected. The ratio and total numbers of NK cells and their terminal mature cell subset (KLRG1+ and Ly49H+ NK cells) were reduced compared with those in control mice on day 7 but not day 21 postinfection. DHA feeding resulted in higher IFN-γ and granzyme B expression in splenic NK cells on day 7 postinfection. A mechanistic analysis showed that the splenic NK cells of DHA-fed mice showed enhanced glucose uptake, increased CD71 and CD98 expression, and higher mitochondrial mass and activity than those of control mice. In addition, DHA-fed mice showed reductions in the total numbers and activation of CD4+ and CD8+ T cells. Conclusions These results suggest that DHA supplementation represses the early response to CMV infection but preserves NK cell effector functions by improving mitochondrial activity, which may play critical roles in subsequent MCMV clearance.