Papel da proteína de superfície SAG2A de Toxoplasma gondii na regulação da resposta imune inata de hospedeiros murinos

Abstract

Toxoplasma gondii is known to shut down pro-inflammatory responses triggered by Toll-like receptor agonists and, in this sense, has been widely used as a model for subversion of innate immunity. Here, we describe one of the possible mechanisms by which the parasite is able to down regulate nitric oxide and IL-12 production by activated macrophages and dendritic cells. We show that parasite-induced immunomodulation is independent of live invasion and replication, and presented distinct patterns depending on the type of strain used (type I or II). Strikingly, blockage of SAG2A surface protein by specific monoclonal antibody reverted the suppression of activated cells in a dose-dependent manner. Further analysis indicated that the innate immune modulation induced by the molecule depends on the presence of the intact Cterminal region of the protein. Additionally, in silico analysis revealed that the protein presents diverse phosphorylation sites of hosts intracellular kinases and cAMP, in addition to an orthologue of the human IL-6 binding site at the cytokine α−chain receptor, which is shown to actively bind the cytokine. Altogether, we demonstrate that SAG2A by T. gondii is able to modulate innate immune responses and contributes to parasite evasion of effectors mechanisms induced by the host.