The Acute Phase ofTrypanosoma cruziInfection 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 ofTrypanosoma cruziinfection 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 PGE2synthesis; 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-γand low quantities of IL-10; and greater numbers of CD8+CD44highCD62Llowmemory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTB4/LTC4, 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 ofT. cruziinfection.