The acute phase of trypanosoma cruzi infection is attenuated in 5-lipoxygenase-deficient mice

Abstract

In the present work we examine the contribution of 5-lipoxygenase- (5-LO-) derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout (5-LO-/-) mice and wild-type (WT) mice. Compared with WT mice, the 5-LO-/- mice developed less parasitemia/tissue parasitism, less inflammatory cell infiltrates, and a lower mortality. This resistance of 5-LO-/- mice correlated with several differences in the immune response to infection, including reduced PGEsynthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL)-12 early in the infection; enhanced splenocyte production of IL-1β, IL-6, and IFN-γ; rapid T-cell polarization to secrete high quantities of IFN-γ and low quantities of IL-10; and greater numbers of CD8+ C D 4 4 h i g h C D 62 L l o w memory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTBLTC T cell bias to produce IFN-γ, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. These data also provide evidence that 5-LO-derived mediators negatively affect host survival during the acute phase of T. cruzi infection.