Incorporation of a dietary omega 3 fatty acid impairs murine macrophage responses to Mycobacterium tuberculosis.
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 IFNgamma-mediated signaling pathway.


RESULTS
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 IFNgamma, 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 (TNFalpha, IL-6 and MCP-1), and lower expression of co-stimulatory molecules (CD40 and CD86). DHA treatment impaired STAT1 phosphorylation and colocalization of the IFNgamma receptor with lipid rafts, without affecting surface expression of IFNgamma receptor.


CONCLUSIONS
We conclude that DHA reduces the ability of J774A.1 cells to control M. tuberculosis in response to activation by IFNgamma, by modulation of IFNgamma receptor signaling and function, suggesting that n-3 PUFA-enriched diets may have a detrimental effect on host immunity to tuberculosis.
Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, College Station, Texas, United States of America. bonilla@bcm.edu
Diana L
DL
Bonilla
Lan H
LH
Ly
Yang-Yi
YY
Fan
Robert S
RS
Chapkin
David N
DN
McMurray
D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002460:Cell Line; D004041:Dietary Fats / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology*; D008563:Membrane Lipids / Q000378:metabolism; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014376:Tuberculosis / Q000382:microbiology; D000096743:Interferon gamma Receptor
D051940:B7-2 Antigen; D015415:Biomarkers; D019013:CD40 Antigens; D004041:Dietary Fats; D004281:Docosahexaenoic Acids; D008563:Membrane Lipids; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor