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 a component of innate immunity critical for controlling CMV infection, the current study explored the effect of a DHA-enriched diet on susceptibility to murine (M) CMV infection and the NK cell effector response to MCMV 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 at day 7 postinfection, but final MCMV clearance was not affected. The total numbers of NK cells and their terminal mature cell subset (KLRG1+ and Ly49H+ NK cells) were reduced compared with those in control mice at day 7 postinfection but not day 21. DHA feeding resulted in higher IFN-γ and granzyme B expression in splenic NK cells at day 7 postinfection. A mechanistic analysis showed that the splenic NK cells of DHA-fed mice had enhanced glucose uptake, increased CD71 and CD98 expression, and higher mitochondrial mass than control mice. In addition, DHA-fed mice showed reductions in the total numbers and activation levels 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.

Docosahexaenoic acid-loaded chitosan/alginate membrane reduces biofilm formation by P. aeruginosa and promotes MSC-mediated burn wound healing

“…23 In contrast to previous studies, we detected no antibacterial activity at different concentrations of DHA in vitro (Figure 4(a)). Studies have shown a reduction in the number of bacteria (quantified as CFU log) in vivo 23,24 Consistently, our observation in bacterial viability analysis (Figure 4(c)) indicated that the CA-DHA-MSC membrane had a relatively higher antibacterial activity in vivo compared to other membrane formulations and the control group. This phenomenon can be partly related to the activation of the innate immune response, including macrophage-and NK cellsmediated responses, accelerating the clearance of pathogens.…”

“…This phenomenon can be partly related to the activation of the innate immune response, including macrophage- and NK cells-mediated responses, accelerating the clearance of pathogens. 24

Figure 4.The antibacterial and antibiofilm activities of composite scaffolds. (A) The in vitro antibacterial activity of the CA and composite scaffolds was assessed using the disk diffusion agar method.

…”

“…This phenomenon can be partly related to the activation of the innate immune response, including macrophage-and NK cellsmediated responses, accelerating the clearance of pathogens. 24 Wound infection promotes local chronic inflammation, which may lead to treatment failure. In the present study, we evaluated the effects of different composite membranes on the healing process of burn wounds infected with P. aeruginosa, which is the most important opportunistic pathogen causing burn wound infections, especially in hospitalized patients.…”

The ω-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid Enhances NK-Cell Antitumor Effector Functions

“…C57BL/6J- Rag2 em3Lutzy /J ( Rag2 −/− ) and B6N.129(FVB)- Ppargc1a ( PGC-1α ) tm2.1Brsp /J ( PGC1α fl/fl ) mice were purchased from The Jackson Laboratory (Sacramento); Ncr1 -Cre (C57BL/6- Ncr1 tm1(iCre)/Bcgen) mice were a kind gift from Beijing Biocytogen (Beijing, China); and 8-week-old wild-type (WT) C57BL/6J mice (approximately 22–25 g) were purchased from Hunan Sja Laboratory Animal Co., Ltd. The mice were divided into two groups as described previously ( 15 ). The DHA supplementation group was fed a diet containing DHA (2.48% DHA, D201124, Dyets Biotechnology Ltd), and the control group was fed a control diet [D200208, Dyets Biotechnology (Wu Xi) Ltd.; Supplementary Table S1].…”

“…In mouse models, ω-3 PUFA–rich fish oil was found to impair spleen but not lung NK-cell activity in mice infected with influenza ( 13 ), whereas other studies have shown that dietary DHA promotes the activation of splenic NK cells ( 5, 14 ). Recently, we found that DHA feeding resulted in a reduced frequency of NK cells in the blood of mice but an enhanced capacity for IFNγ production by NK cells and enhanced NK-cell cytotoxicity during murine cytomegalovirus (MCMV) infection ( 15 ). NK cell–derived IFNγ is a pivotal factor that sustains tumor dormancy, thereby preventing tumor metastasis to the liver and lung ( 16, 17 ).…”