Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Infection.

Arginase-1 (Arg-1) is a marker for alternatively activated macrophages (AAM) and is mainly induced by the type 2 cytokines interleukin (IL)-4 and IL-13 through the common IL-4 receptor-alpha (Rα) subunit. Both, Arg-1 and AAM undermine macrophage effector functions against intracellular parasites and are therefore implicated in the susceptibility to infection with , the causative agent of Chagas' disease. However, the involvement of Arg-1 in promoting intracellular replication of in AAM has not been proven so far . Because Arg-1 is only moderately expressed in -infected wildtype mice, we elucidated the role of Arg-1 and AAM during infection in IL-13-overexpressing (IL-13) mice, which are characterized by an inflammation-induced development of AAM and an accompanied elevated expression of Arg-1. In comparison to wildtype littermates, IL-13 mice were highly susceptible to infection with enhanced parasitemia and impaired survival. Importantly, -infected IL-13 mice developed an elevated alternative macrophage activation with increased arginase activity. To proof the hypothesis, that Arg-1 accounts for the increased susceptibility of IL-13 mice, we blocked arginase activity in infected IL-13 mice. Because this arginase inhibition resulted in a decreased susceptibility to experimental Chagas disease our study supports in summary the conclusion that IL-13/IL-4Rα-driven Arg-1 expression contributes to the permissiveness of the host to infection.