Defining neuronal responses to the neurotropic parasite Toxoplasma gondii

A select group of pathogens infect neurons in the brain. Prior dogma held that neurons were "defenseless” against infecting microbes, but many studies suggest that neurons can mount anti-microbial defenses. However, a knowledge gap in understanding how neurons respond in vitro and in vivo to different classes of micro-organisms remains. To address this gap, we compared a transcriptional dataset derived from primary neuron cultures (PNCs) infected with the neurotropic intracellular parasite Toxoplasma gondii with a dataset derived from neurons injected with T. gondii protein in vivo. These curated responses were then compared to the transcriptional responses of PNCs infected with the single stranded RNA viruses West Nile Virus (WNV) or Zika Virus (ZKV). These analyses highlighted a conserved response to infection associated with chemokines (Cxcl10, Ccl2) and cytokines (interferon signaling). However, T. gondii had diminished IFN-α signaling in vitro compared to the viral datasets and was uniquely associated with a decrease in neuron-specific genes (Snap25, Slc17a7, Prkcg). These data underscore that neurons participate in infection-induced neuroinflammation and illustrate that neurons possess both pathogen-specific and pathogen-conserved responses. RNA seq profiling of E174 cortical neurons harvested from Ai6(RCL-ZsGreen) mice. Ten days post harvest, neurons were either infected with an MOI of 5 of type II (Prugniaud (PRU)) Toxoplasma gondii or left uninfected. RNA was harvested 24 hpi. Three biological replicates were performed for 3 samples of infected, primary cortical neurons and 3 samples of uninfected primary cortical neurons.