Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to balance immunotherapy and susceptibility to infection

Abstract

Polyunsaturated fatty acids (PUFAs), notably of the n-3 series, have immunosuppressive effects which make these molecules candidates for treating inflammatory symptoms associated with cardiovascular disease, obesity, arthritis, and asthma. However, immunosuppression by PUFAs could increase susceptibility to bacterial and viral infection. A detailed molecular picture is required in order to understand the balance between the benefits and risks of utilizing PUFAs as adjuvant immunosuppressants. Here we review evidence that incorporation of PUFAs into membrane lipids of antigen-presenting cells (APCs) downregulates APC function. We propose that PUFAs modulate antigen presentation by altering the organization of lipid and protein molecules of the plasma membrane and endomembranes; this alters recognition and responses by T cells. The foundation of our hypothesis is built on data from artificial bilayer experiments which provide the physical principles by which PUFA acyl chains affect membrane architecture. This review also reconciles conflicting results in the literature by discussing the advantages and disadvantages of differing methods of PUFA treatment of cells. We suggest that membrane modulation of immune cells may be an important and overlooked mechanism of immunomodulation. In addition, we propose that mechanistic studies with defined experimental protocols will speed the translation of laboratory studies on PUFAs to the clinic.

Rapid adaptation of Rhodococcus erythropolis cells to salt stress by synthesizing polyunsaturated fatty acids

“…Additionally, the multiple double bonds in these fatty acids may influence the bilayer organisation of membranes including, e.g. lateral pressure, microviscosity, curvature, permeability and elasticity which affect membrane proteins (Shaikh and Edidin 2008). PUFAs can also promptly inhibit sodium ion channels, which may be used to prevent cardiac arrhythmias in mammals (Xiao et al 1995;Xiao et al 2005).…”

Effects of dietary fish meal and soybean meal on the ovine innate and acquired immune response during pregnancy and lactation

“…Given the association between n-3 FA : n-6 FA ratio and a growing number of human diseases, health conscious consumers have begun supplementing their diets with fish oil capsules and/or fortified products containing n-3 FA (Shaikh and Edidin, 2008). In order to meet this niche market, numerous -E-mail: nkarrow@uoguelph.ca livestock producers have been incorporating n-3 FA enriched supplements such as fish meal (FM) into livestock diets to produce 'value-added products' like n-3 FA enriched milk (Gó mez-Cortés et al, 2009).…”

The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders

“…EPA and DHA integration into lymphocyte membranes provokes changes in fluidity, suppression of signal transduction and inhibition of T cell proliferation and apoptosis [76,147]. There is also considerable evidence demonstrating that increased levels in the membranes of antigen-presenting cells decrease their function and impair T cell recognition of antigens [147]. DHA and EPA inhibit the maturation of dendritic cells and change their pattern of cytokine production by inhibiting the production of IL-12 and stimulating the synthesis of IL-10 [148].…”

“…n-3 PUFA-induced TLR-4 inhibition can also result from incorporation of DHA into MLRs disrupting the lateral translocation of the TLR-4 protein into the domains and, hence, inhibiting the signalling pathway leading to downregulation of NF-κB production [145,146]. EPA and DHA integration into lymphocyte membranes provokes changes in fluidity, suppression of signal transduction and inhibition of T cell proliferation and apoptosis [76,147]. There is also considerable evidence demonstrating that increased levels in the membranes of antigen-presenting cells decrease their function and impair T cell recognition of antigens [147].…”