Paradoxical role of eicosanoids during Mycobacterium tuberculosis infection

Eicosanoids constitute a group of potent biologically active lipid metabolites, controlling the immune response. During the last years, some studies about the functions of lipid mediators had restricted not only to their participation in inflammatory responses but also as mediators able to modulate the pathogenesis of infections. However, the influence of those eicosanoids in tuberculosis (TB) remains ambiguous. To appreciate specifically the effect of LTB4 in TB, we infected 5-LO-/- and the WT (sv129) mice with Mycobacterium tuberculosis (Mtb) and supplemented intranasal with LTB4 (formulated in PLGA microsphere) or pharmacology inhibition of COX-2. Our results demonstrated that LTB4 reposition increased the susceptibility of 5-LO-/- mice, altering the inflammatory scenario and inducing elevated lung inflammation, necrosis and tissue damage. However, inhibition of COX-2 improved innate immune response, independently of LTB4 background levels. For this reason, pharmacology modulation of eicosanoid production can be important host-directed therapy in TB.