Arginase in Parasitic Infections: Macrophage Activation, Immunosuppression, and Intracellular Signals

Abstract EN

A type 1 cytokine-dependent proinflammatory response inducing classically activated macrophages (CaMϕs) is crucial for parasite control during protozoan infections but can also contribute to the development of immunopathological disease symptoms.

Type 2 cytokines such as IL-4 and IL-13 antagonize CaMϕs inducing alternatively activated macrophages (AaMϕs) that upregulate arginase-1 expression.

During several infections, induction of arginase-1-macrophages was showed to have a detrimental role by limiting CaMϕ-dependent parasite clearance and promoting parasite proliferation.

Additionally, the role of arginase-1 in T cell suppression has been explored recently.

Arginase-1 can also be induced by IL-10 and transforming growth factor-β (TGF-β) or even directly by parasites or parasite components.

Therefore, generation of alternative activation states of macrophages could limit collateral tissue damage because of excessive type 1 inflammation.

However, they affect disease outcome by promoting parasite survival and proliferation.

Thus, modulation of macrophage activation may be instrumental in allowing parasite persistence and long-term host survival.