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Transgenic Mice Enriched in Omega-3 Fatty Acids Are More Susceptible to Pulmonary Tuberculosis: Impaired Resistance to Tuberculosis in fat-1 Mice
Diana L. Bonilla, Yang-Yi Fan, Robert S. Chapkin and David N. McMurray
The Journal of Infectious Diseases
Vol. 201, No. 3 (1 February 2010), pp. 399-408
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/27794432
Page Count: 10
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Background. Besides their health benefits, dietary omega-3 fatty acids (n-3 PUFAs) can impair host resistance to intracellular pathogens. Previously, we and others have showed that n-3 PUFA–treated macrophages poorly control Mycobacterium tuberculosis infection in vitro. Methods. Wild-type and fat-1 transgenic mice were infected with virulent H37Rv M. tuberculosis via the aerosol route. We evaluated bacteriological and histopathological changes in lungs, as well as differences in activation and antimycobacterial capacity in primary macrophages ex vivo. Results. fat-1 mice were more susceptible to tuberculosis, as demonstrated by higher bacterial loads and less robust inflammatory responses in lungs. Macrophages obtained from fat-1 mice were more readily infected with M. tuberculosis in vitro, compared with wild-type macrophages. This imparied bacterial control in cells from fat-1 mice correlated with reduced proinflammatory cytokine secretion, impaired oxidative metabolism, and diminshed M. tuberculosis–lysotracker colocalization within phagosomes. Conclusions. We showed that endogenous production of n-3 PUFAs in fat-1 mice increases their susceptibility to tuberculosis, which could be explained in part by diminished activation and antimycobacterial responses in cells from fat-1 mice. These data suggest that n-3 PUFA–supplemented diets might have a detrimental effect on immunity to M. tuberculosis and raise concerns regarding the safety of omega-3 dietary supplementation in humans.
The Journal of Infectious Diseases © 2010 Oxford University Press