PLoS One. 2014 Feb 5;9(2):e88398. doi: 10.1371/journal.pone.0088398. eCollection 2014.
Differential Induction of TLR3-Dependent Innate Immune Signaling by Closely Related Parasite Species
Beiting DP1, Peixoto L1, Akopyants NS2, Beverley SM2, Wherry EJ3, Christian DA4, Hunter CA4, Brodsky IE4, Roos DS1.
The closely related protozoan parasites Toxoplasma gondii and Neospora caninum display similar life cycles, subcellular ultrastructure, invasion mechanisms, metabolic pathways, and genome organization, but differ in their host range and disease pathogenesis. Type II (γ) interferon has long been known to be the major mediator of innate and adaptive immunity to Toxoplasma infection, but genome-wide expression profiling of infected host cells indicates that Neospora is a potent activator of the type I (α/β) interferon pathways typically associated with antiviral responses. Infection of macrophages from mice with targeted deletions in various innate sensing genes demonstrates that host responses to Neospora are dependent on the toll-like receptor Tlr3 and the adapter protein Trif. Consistent with this observation, RNA from Neospora elicits TLR3-dependent type I interferon responses when targeted to the host endo-lysosomal system. Although live Toxoplasma fail to induce type I interferon, heat-killed parasites do trigger this response, albeit much weaker than Neospora, and co-infection studies reveal that T. gondii actively suppresses the production of type I interferon. These findings reveal that eukaryotic pathogens can be potent inducers of type I interferon and that related parasite species interact with this pathway in distinct ways.
- [PubMed - in process]