Incorporation of a Dietary Omega 3 Fatty Acid Impairs Murine Macrophage Responses to Mycobacterium tuberculosis
Incorporation of a Dietary Omega 3 Fatty Acid Impairs Murine Macrophage Responses to Mycobacterium tuberculosis
复制标题
DOI：
10.1371/journal.pone.0010878
复制
发表时间：
2010-05-28
期刊：
影响因子：
3.7
通讯作者：
McMurray, David N.
中科院分区：
文献类型：
--
作者：
Bonilla, Diana L.;Ly, Lan H.;McMurray, David N.
背景资料：除了它们的健康益处之外，膳食ω 3多不饱和脂肪酸（n-3 PUFA）可能通过创造免疫抑制环境而损害宿主对结核分枝杆菌（Mtb）的抵抗力。我们假设，n-3 PUFA的掺入抑制激活巨噬细胞抗分枝杆菌的反应，有利于细菌生长，部分，通过调节IFN γ介导的信号转导pathway.Methodology/Principal Findings：小鼠巨噬细胞样J774A.1细胞与牛血清白蛋白（BSA）共轭二十二碳六烯酸（DHA; 22：6 n-3）或BSA单独孵育，用重组IFN γ激活，并感染M的强毒株（H37 Rv）。结核巨噬细胞膜的脂肪酸组成被DHA处理显著改变。DHA处理的巨噬细胞在控制细胞内分枝杆菌方面效果较差，并表现出氧化代谢受损和吞噬溶酶体成熟减少。DHA的掺入导致有缺陷的巨噬细胞活化，其特征在于促炎细胞因子（TNF α、IL-6和MCP-1）的产生减少，以及共刺激分子（CD 40和CD 86）的表达降低。DHA治疗损害STAT 1磷酸化和共定位的IFN γ受体与脂筏，而不影响表面表达的IFN γ receptor.Conclusions/Significance：我们得出结论，DHA降低J774A.1细胞控制M。通过调节IFN γ受体的信号传导和功能，证实了富含n-3 PUFA的饮食可能对宿主对结核病的免疫力具有不利影响。
Background: Beside their health benefits, dietary omega 3 polyunsaturated fatty acids (n-3 PUFA) might impair host resistance to Mycobacterium tuberculosis (Mtb) by creating an immunosuppressive environment. We hypothesized that incorporation of n-3 PUFA suppresses activation of macrophage antimycobacterial responses and favors bacterial growth, in part, by modulating the IFN gamma-mediated signaling pathway.Methodology/Principal Findings: Murine macrophage-like J774A.1 cells were incubated with bovine serum albumin (BSA)-conjugated docosahexaenoic acid (DHA; 22:6n-3) or BSA alone, activated with recombinant IFN gamma, and infected with a virulent strain (H37Rv) of M. tuberculosis. The fatty acid composition of macrophage membranes was modified significantly by DHA treatment. DHA-treated macrophages were less effective in controlling intracellular mycobacteria and showed impaired oxidative metabolism and reduced phagolysosome maturation. Incorporation of DHA resulted in defective macrophage activation, as characterized by reduced production of pro-inflammatory cytokines (TNF alpha, IL-6 and MCP-1), and lower expression of co-stimulatory molecules (CD40 and CD86). DHA treatment impaired STAT1 phosphorylation and colocalization of the IFN gamma receptor with lipid rafts, without affecting surface expression of IFN gamma receptor.Conclusions/Significance: We conclude that DHA reduces the ability of J774A.1 cells to control M. tuberculosis in response to activation by IFN gamma, by modulation of IFN gamma receptor signaling and function, suggesting that n-3 PUFA-enriched diets may have a detrimental effect on host immunity to tuberculosis.