T cell intrinsic role of Nod2 in promoting type I immunity against Toxoplasma gondii

Nod2 belongs to the (NOD)-like receptor (NLR) family of proteins, which function as intracellular pathogen sensors in innate immune cells. Nod2-deficiency results in an impaired immune response against bacterial pathogens. However, our understanding of how this protein promotes host defense against intracellular parasites is unknown. Here we found that Nod2(−/−) mice showed reduced clearance of Toxoplasma gondii and decreased interferon-γ production. Reconstitution of T-cell deficient mice with Nod2(−/−) T cells followed by T. gondii infection revealed a T cell-intrinsic defect. Nod2(−/−) CD4(+) T cells displayed poor helper T cell differentiation, which was associated with impaired IL-2 production and nuclear accumulation of c-Rel. These data revealed a T cell-intrinsic role of Nod2 signaling that is critical for host defense against T. gondii.