Fatty Obstacle to TB Immunity

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Science  08 Jul 2005:
Vol. 309, Issue 5732, pp. 222
DOI: 10.1126/science.309.5732.222d

Immunopathology caused by the chronic production of inflammatory cytokines is normally avoided through a number of counterinflammatory pathways. Some of these depend on lipid mediators known as lipoxins, including lipoxase A4 (LXA4), which is derived via 5-lipoxygenase (5-LO)-mediated biosynthesis.

Bafica et al.explored whether the 5-LO pathway might influence the course of experimental M. tuberculosis infection, and found that LXA4 was indeed generated at significant levels in the sera of infected mice. Genetic deficiency in 5-LO increased the ability of animals to control infection, with a reduction in bacterial counts and increase in survival of animals after infection. This was accompanied by amplification of hallmark inflammatory cytokines, including IFN-γ and IL-12, as well as nitric oxide synthase 2, which is an important factor in host resistance to M. tuberculosis. Treatment of 5-LO-deficient mice with a lipoxin analog reversed resistance. 5-LO is already being assessed as a therapeutic target in asthma, and this study suggests that 5-LO inhibition may also help to control chronic infectious diseases. — SJS

J. Clin. Invest. 115, 1601 (2005).

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