Abstract
BackgroundBeside 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 IFNγ-mediated signaling pathway.Methodology/Principal FindingsMurine 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 IFNγ, 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 (TNFα, IL-6 and MCP-1), and lower expression of co-stimulatory molecules (CD40 and CD86). DHA treatment impaired STAT1 phosphorylation and colocalization of the IFNγ receptor with lipid rafts, without affecting surface expression of IFNγ receptor.Conclusions/SignificanceWe conclude that DHA reduces the ability of J774A.1 cells to control M. tuberculosis in response to activation by IFNγ, by modulation of IFNγ receptor signaling and function, suggesting that n-3 PUFA-enriched diets may have a detrimental effect on host immunity to tuberculosis.
Highlights
Tuberculosis (TB), a bacterial disease caused by Mycobacterium tuberculosis (Mtb), continues as a public health problem [1]
docosahexaenoic acid (DHA) treatment alters lipid membrane composition J774A.1 cells efficiently incorporate fatty acids provided in the culture medium into their cell membranes under the conditions used in this study
We demonstrated that IFNc-activated macrophage-like J774A.1 cells treated with DHA exhibited impairment in several indicators of cell activation and increased susceptibility to virulent Mtb infection
Summary
Tuberculosis (TB), a bacterial disease caused by Mycobacterium tuberculosis (Mtb), continues as a public health problem [1] Host resistance to this pathogen requires the development of an effective cellular immune response, mediated mainly by T cells and macrophages [1]. The activation of these cells can be modulated by nutritional components, such as carbohydrates, proteins and vitamins, impacting subsequently on the resistance to TB [2,3,4]. The role of distinct classes of long chain dietary fatty acids during TB infection has not been well investigated to date 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 IFNc-mediated signaling pathway
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
