December 2012

How high cholesterol levels come in handy during protozoan infection

Cover of the December 2012 issue of the Journal of Lipid Research

It has been long impressed on us by doctors and news reports that eating too much fatty food will lead to hyperlipidemia and, worse, potentially deadly atherosclerosis and cardiovascular disease. Statins, now being prescribed by doctors to untold millions of people around the world to reverse these conditions, have made the pharmaceutical industry a multibillion dollar industry. So it is surprising that in the December issue of the Journal of Lipid Research, researchers in India presented data suggesting that hyperlipidemia confers some protection against leishmaniasis, a disease caused by protozoan parasite infection.

JLR Associate Editor Kenneth R. Feingold and editorial board member Carl Grunfeld of the Department of Veterans Affairs Medical Center at the University of California, San Francisco, review the previous literature and this article in a special commentary.

The innate immune system is the nonspecific first line of defense the human body has against infection by foreign invaders. Part of this immune system are Toll-like receptors; present on the surface of macrophages and other cells, they activate this innate response when they recognize conserved products from microbes. Leishmania donovani is transmitted by the bite of the sand fly. The protozoan survives in infected individuals by living in macrophages, depleting cholesterol and disrupting lipid rafts, thus hampering the macrophage’s usual action in the innate response of alerting the body to an invader by antigen presentation.

In an article entitled “Hyperlipidemia offers protection against Leishmania donovani infection: role of membrane cholesterol,” June Ghosh of the Indian Institute of Chemical Biology and colleagues present data demonstrating that hyperlipidemia protects from leishmaniasis. In a mouse model, apolipoprotein E knockout mice showed a marked decrease in splenic and liver parasite burden six weeks post-Leishmania infection; in contrast, the parasitic burden in wild-type infected mice continued to increase as time went on. Mice fed an atherogenic diet also resisted the spread of infection better than mice fed a normal diet, and as might be expected, when mice received statin treatment, which decreases serum lipid levels, their susceptibility to infection increased. Taken together with previous studies in hamsters, Feingold and Grunfeld suggest these data provide convincing evidence that serum cholesterol levels are important to modulating Leishmania donovani infection. While some microorganisms have been able to use host lipid and lipoproteins to their advantage to survive, the results presented in the article by Ghosh et al. suggest that a carefully balanced approach in adjusting serum lipid levels could be the key to providing protection from Leishmania.
 

Mary L. ChangMary L. Chang (mchang@asbmb.org) is managing editor of the Journal of Lipid Research and coordinating journal manager of the journal Molecular & Cellular Proteomics.
 
 


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