Interferon-gamma- and perforin-mediated immune responses for resistance againstToxoplasma gondiiin the brain

Abstract

Toxoplasma gondiiis an obligate intracellular protozoan parasite that causes various diseases, including lymphadenitis, congenital infection of fetuses and life-threatening toxoplasmic encephalitis in immunocompromised individuals. Interferon-gamma (IFN-γ)-mediated immune responses are essential for controlling tachyzoite proliferation during both acute acquired infection and reactivation of infection in the brain. Both CD4+and CD8+T cells produce this cytokine in response to infection, although the latter has more potent protective activity. IFN-γcan activate microglia, astrocytes and macrophages, and these activated cells control the proliferation of tachyzoites using different molecules, depending on cell type and host species. IFN-γalso has a crucial role in the recruitment of T cells into the brain after infection by inducing expression of the adhesion molecule VCAM-1 on cerebrovascular endothelial cells, and chemokines such as CXCL9, CXCL10 and CCL5. A recent study showed that CD8+T cells are able to removeT. gondiicysts, which represent the stage of the parasite in chronic infection, from the brain through their perforin-mediated activity. Thus, the resistance to cerebral infection withT. gondiirequires a coordinated network using both IFN-γ- and perforin-mediated immune responses. Elucidating how these two protective mechanisms function and collaborate in the brain againstT. gondiiwill be crucial in developing a new method to prevent and eradicate this parasitic infection.