Arginase in parasitic infections: macrophage activation, immunosuppression, and intracellular signals.
A type 1 cytokine-dependent proinflammatory response inducing classically activated macrophages (CaMvarphis) 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 CaMvarphis inducing alternatively activated macrophages (AaMvarphis) that upregulate arginase-1 expression. During several infections, induction of arginase-1-macrophages was showed to have a detrimental role by limiting CaMvarphi-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-beta (TGF-beta) 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.
Stempin
Cinthia C
CC
Inmunología, CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina.
Dulgerian
Laura R
LR
Garrido
Vanina V
VV
Cerban
Fabio M
FM
D000818:Animals; D001119:Arginase / Q000276:immunology*; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D010272:Parasitic Diseases / Q000201:enzymology* / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D001119:Arginase