EATING the right kind of fat might help people with tuberculosis conquer the disease. But consuming the wrong kinds of fats, especially fish oils, could help TB bacteria evade destruction.
That is the picture emerging from experiments with macrophages, the white blood cells that normally engulf and destroy invading microbes. After overwhelming the bacteria, macrophages trap them in a chamber inside the cell called a phagosome. This then fuses with another chamber, called a lysosome, which contains digestive enzymes that destroy the invader (see Graphic).
But this does not happen when Mycobacterium tuberculosis is engulfed. 鈥淭his bug has learned a trick to block fusion with the lysosome,鈥� says Gareth Griffiths of the European Molecular Biology Laboratory in Heidelberg, Germany. Instead, the bacteria begin multiplying inside the phagosome, turning the cells meant to destroy them into hiding places where they are protected from further immune attack. This is one of the reasons TB is so hard to treat, requiring a minimum of 6 months on antibiotics. Microbiologists have been puzzling for years over how exactly the bacterium hijacks macrophages.
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In experiments on mouse macrophages growing in the lab, Griffiths鈥檚 team has now shown that some fats restore the ability of phagosomes to fuse with lysosomes and destroy their stowaways. Arachidonic acid proved the most potent, followed by ceremide, an edible fat often used in face creams. Others include sphingomyelin and sphyngosine-1-phosphate.
These fats appear to work by kick-starting the production of actin, the building block of the filaments that form the internal skeleton of cells. Phagosomes have to sprout actin filaments to provide a 鈥渢rackway鈥� along which a lysosome can travel towards the phagosome, Griffiths thinks. Without the filaments, the two bodies cannot fuse.
The more actin macrophages produced, the more potent their killing power, Griffiths鈥� team reports in Nature Cell Biology (DOI: 10.1038/ncb1036). His hunch is that fats such as ceremide override chemical signals from M. tuberculosis that tell the phagosome to stop maturing, which blocks formation of the actin trackways.
The bad news is that the team found that the omega-3 fatty acids and eicosapentaenoic acids abundant in fish oils inhibit production of actin, making it easier for the bugs to survive and multiply. This tallies with studies that show that Inuit on fish-rich diets are unusually susceptible to TB, Griffiths says.
Most of the seven anti-TB fats identified abound in animal and vegetable oils and fats, and could easily be incorporated into pills or capsules in optimum combinations. Griffiths says there are good reasons to believe that eating anti-TB fats will have the same effects as giving them to cells directly. He hopes that giving TB patients capsules of the fats along with the usual course of antibiotics, as well as advising them to avoid the 鈥渨rong鈥� fats, could speed up treatments.