Toxoplasma type II effector GRA15 has limited influence in vivo

Area of Science:

• Immunology
• Parasitology
• Neuroscience

Background:

• Toxoplasma gondii is an intracellular parasite causing chronic brain infections.
• Parasite effector proteins manipulate host cells; GRA15 is a polymorphic effector influencing host signaling.
• The precise role of GRA15 in chronic brain infection and host immunity remains unclear.

Purpose of the Study:

• To investigate the impact of the GRA15 effector protein on Toxoplasma gondii brain parasite burden and host immune responses in vivo.
• To compare infection outcomes in mice infected with wild-type (WT) and a GRA15-deficient (IIΔgra15) Toxoplasma strain.

Main Methods:

• Generation of a IIΔgra15 Toxoplasma gondii strain.
• Infection of mice with WT and IIΔgra15 strains.
• Analysis of brain parasite burden, and immune cell populations (macrophages, microglia, T cells, NK cells) in the brain and spleen at 3 weeks post-infection.

Main Results:

• No significant difference in brain parasite burden or parenchymal immune cell numbers (macrophages, microglia, T cells) between WT and IIΔgra15 infected mice.
• IIΔgra15 infected mice showed reduced splenic M1-like macrophages and altered frequencies of specific T cell subsets (PD-1+ CTLA-4+ CD4+) and NK cells compared to WT.
• Equivalent IFN-γ+ CD4 and CD8 T cell populations were observed in both groups.

Conclusions:

• GRA15 has a subtle influence on the peripheral immune response in Toxoplasma gondii infected mice.
• This subtle effect does not significantly alter brain parasite burden or the number of immune cells within the brain parenchyma at 3 weeks post-infection.