Human neuronal cells SH-SY5Y as an in vitro model to study Neospora caninum infection and innate immune modulation

Neospora caninum causes significant losses due to abortions in cattle worldwide. The parasite can establish persistent infections in the central nervous system (CNS). Innate immune recognition, primarily mediated by Toll-like receptors (TLRs), and the expression of cytokines and antimicrobial peptides, such as cathelicidins, during N. caninum infection in neuronal cells remains undefined. This work studied the ability of N. caninum to infect and replicate in the CNS using an in vitro model for neurotropic infections in human neuroblastoma (SH-SY5Y) cells. We showed that N. caninum established productive infections in SH-SY5Y cells, and that the parasite can invade, replicate, and cause cell lysis. Infections with N. caninum induced a time-dependent modulation of the key components of innate immunity, TLR7 and CAMP, in SH-SY5Y cells. At the onset (24 h post-infection), N. caninum decreased TLR7 expression, while CAMP expression was increased. The TLR7-dependent signalling pathway modulated by N. caninum infection included increased MyD88 expression and decreased IRF7 expression. In conclusion, the human neuroblastoma cell line SH-SY5Y was susceptible to N. caninum infection and showed modulation of the innate immune response during infection.