Innate immunity to Toxoplasma gondii infection

Toxoplasma gondii is a protozoan parasite that infects more than 1 billion people in the world. In addition to humans, T. gondii can infect all mammals and birds. Mice are a natural host for T. gondii and are a thoroughly studied animal model for T. gondii infection.In mice, Toll-like receptor 11 (TLR11) is the principal innate immune sensor for T. gondii. TLR11 recognizes the unconventional actin-binding protein profilin, which is essential for parasite invasion into host cells.In humans, TLR11 is a nonfunctional pseudogene. Consequently, the mechanisms through which the human immune system recognizes T. gondii are not well understood. Additional TLRs, in particular TLR2, TLR7 and TLR9, as well as the NLRP1 (NOD-, LRR- and pyrin domain-containing 1) inflammasome are all possible candidates for innate immune sensors that could be involved in human defence against T. gondii.In a mouse model, activation of TLR11 and myeloid differentiation primary-response protein 88 (MYD88) in dendritic cells leads to the induction of interleukin-12 (IL-12) expression and the activation of interferon-γ (IFNγ) production by natural killer (NK) cells. In addition, both CD4+ T cell-derived and CD8+ T cell-derived IFNγ is essential for host resistance to the parasite.An emerging source of IFNγ that does not require TLR-mediated parasite recognition is the neutrophil.IFNγ mediates host protection via multiple mechanisms including induction of immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs). IFNγ also triggers the induction of the antimicrobial molecules nitric oxide and reactive oxygen species and is responsible for changes in host metabolism that restrict T. gondii replication.