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

Abstract

Toxoplasma gondii is an obligate intracellular protozoan parasite, which 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. Murine models demonstrated that both CD4+ and CD8+ T cells are protective against reactivation of infection, although the latter have more potent protective activity. Various signaling molecules including MyD88, protein kinase C-theta, and nuclear factor-κB family transcription factors are important for T cells in inducing and/or maintaining their protective function. IL-12, IL-4, IL-6, IL-10, IL-17, IL-27, and IL-33 are involved in regulating resistance to T. gondii in the brain. IFN-γ can activate microglia, astrocytes, and macrophages and these activated cells control proliferation of tachyzoites using different molecules depending on the cell types and species of the host. IFN-γ also plays a critical role in recruitment of T cells into the brain after infection by inducing expression of adhesion molecule, VCAM-1, on cerebrovascular endothelial cells and of chemokines such as CXCL9, CXCL10 and CCL5. A recent study revealed that CD8+ T cells are able to remove T. gondii cysts, the stage of the parasite in chronic infection, from the brain through their perforin-mediated activity. Thus, the resistance to cerebral infection with T. gondii requires a coordinated network utilizing both IFN-γ- and perforin-mediated immune responses. Elucidating how these two protective mechanisms function and collaborate in the brain against T. gondii will be crucial in developing a new method to prevent and eradicate this parasitic infection.

Complex Immune Cell Interplay in the Gamma Interferon Response during Toxoplasma gondii Infection

“…IFN-␥ itself increases expression of endothelial vascular cell adhesion molecule 1 (VCAM-1) to aid in recruitment of CD8 ϩ T cells to the brain of chronically infected mice and thus enhances any effects of CD8 ϩ T cells on immunity to T. gondii (45). It seems likely that both IFN-␥ and cytolytic functions of CD8 ϩ T cells are contributing to host resistance to pathogenesis (46). NK cells.…”

CD73-generated adenosine facilitatesToxoplasma gondiidifferentiation to long-lived tissue cysts in the central nervous system

“…We next analyzed gene expression of effector molecules associated with T. gondii infection to determine whether the resistance of CD73 −/− mice was mediated by an increased production of these molecules. IFN-γ is a cytokine critical for controlling T. gondii expansion and reactivation in the brain (25)(26)(27)(28)(29). In WT and CD73…”

Egyptian Propolis 12: Influence of Propolis on Cytokines of Toxoplasma gondii Infected Rats

“…As T. gondii is an obligate intracellular parasite, cellular immunity has been considered the major response to eliminate the parasite within the host, yet humoral immunity also plays an important role in shaping the immune responses (El Fadaly et al, 2012). Suzuki et al, (2011) stated that cytokines secreted in the immune response to T. gondii include upregulated factors (IFNγ, IL-2, TNFα, IL-1, IL-7, IL-12, IL-15) and down regulated factors (IL-4, IL-6, IL-10).…”