Effects of omega-3 and -6 fatty acids on Mycobacterium tuberculosis in macrophages and in mice.
We recently showed that treatment of macrophages prior to Mycobacterium tuberculosis infection with the pro-inflammatory omega-6 lipid, arachidonic acid (AA) enhanced bacterial killing whereas the anti-inflammatory, omega-3 lipid eicosapentaenoic acid (EPA) stimulated bacterial growth. Here we tested if these effects were depending on when lipids were added to macrophages: before or during Mycobacterium smegmatis or M. tuberculosis infection. Collectively, our data suggested that a high omega-6 diet might be beneficial against mycobacteriosis, while a high omega-3 diet might be detrimental. AA also stimulated TNF-alpha secretion in M. tuberculosis-infected macrophages whereas EPA inhibited this process. AA strongly activated the MAP kinase p38 in uninfected cells but M. tuberculosis infected cells blocked the ability of AA to activate p38; AA-dependent killing is therefore independent of p38. We therefore tested diets enriched in omega-3 and omega-6 lipids on a mouse model of tuberculosis. In contrast to the in vitro results, the omega-6 tended to increase survival of M. tuberculosis in mice, while omega-3- tended to increase pathogen killing. Overall our results together with those previously reported in the literature suggest that it is almost impossible to predict, at the whole organism level, if a diet enriched in omega-3 or -6 will be beneficial or detrimental to intracellular pathogens.
Jordao
Luisa
L
Molecular Pathogenesis Centre, Unit of Retrovirus and Associated Infections (CPM-URIA), Faculty of Pharmacy, University of Lisbon, Av. Forcas Armadas, 1600-083 Lisbon, Portugal.
Lengeling
Andreas
A
Bordat
Yann
Y
Boudou
Frederic
F
Gicquel
Brigitte
B
Neyrolles
Olivier
O
Becker
Pablo D
PD
Guzman
Carlos A
CA
Griffiths
Gareth
G
Anes
Elsa
E
D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D054884:Host-Pathogen Interactions; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000254:growth & development; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D048051:p38 Mitogen-Activated Protein Kinases