Transcriptional Analysis Shows a Robust Host Response toToxoplasma gondiiduring Early and Late Chronic Infection in Both Male and Female Mice

Abstract

The long-term host effects caused by the protozoan parasite Toxoplasma gondii are poorly understood. High-throughput RNA sequencing analysis previously determined that the host response in the brain was greater and more complex at 28 days than at 10 days postinfection. Here, we analyzed the host transcriptional profile of age- and sex-matched mice during very early (21 days), early (28 days), mid (3 months), and late (6 months) chronic infection. We found that a majority of the host genes which increase in abundance at day 21 postinfection are still increased at 6 months postinfection for both male and female mice. While most of the differentially expressed genes were similar between sexes, females had far fewer genes that were significantly less abundant, which may have led to the slightly increased cyst burden in males. Transcripts for C-X-C motif chemokine ligand 13 and a C-C motif chemokine receptor 2 (CCR2) were significantly higher in females than in males during infection. As T. gondii chronic infection and profilin (PRF) confer resistance to Listeria monocytogenes infection in a CCR2-dependent manner, the differences in CCR2 expression led us to retest the protection of PRF in both sexes. Male mice were nearly as effective as female mice at reducing the bacterial burden either with a chronic infection or when treated with PRF. These data show that most of the host genes differentially expressed in response to T. gondii infection are similar between males and females. While differences in transcript abundance exist between the sexes, the infection phenotypes tested here did not show significant differences.

Transcriptional profiling reveals T cells cluster around neurons injected withToxoplasma gondiiproteins

“…Collectively, these data are consistent with previous work which has shown upregulated inflammatory pathways and an increase in immune cell infiltrate during infection [48][49][50][51] . Our identification of immune cell transcripts within our "neuron" transcriptomes suggest our samples contain transcripts from nonneuronal cells, such as CD8 + T cells, that were in extremely close proximity to the isolated neurons.…”

“…Why is our identification of immune cell transcripts in the T. gondii-infected brain novel? All prior genome-wide expression studies of the T.gondii-infected CNS have also identified high levels of immune cell or immune response transcripts compared to uninfected brain 48,49,51 . But these studies have all been done using whole brain for RNA isolation, where one would expect to obtain transcripts from all cells within the brain (parenchymal CNS cells and infiltrating immune cells).…”

Transcriptomic Profiling of Mouse Brain During Acute and Chronic Infections by Toxoplasma gondii Oocysts

“…The neuro-pathogenesis of T. gondii infection is driven by a complicated network of molecular processes and pathways (Ngo et al, 2017). Data supporting this view are emerging from various "-omics"-based profiling of the brains of mice infected by T. gondii (Jia et al, 2013;Tanaka et al, 2013;Pittman et al, 2014;Zhou et al, 2015;Hu et al, 2018;Garfoot et al, 2019a;Ma et al, 2019). The magnitude of this challenge has increased the interest in understanding how T. gondii infection affects murine host at the transcriptional level in various tissues other than the brain, including the liver (He et al, 2016a), spleen (He et al, 2016b,c), peripheral lymphocytes (Jia et al, 2013), and the uterus (Zhou et al, 2020).…”

Proteomic and transcriptomic analyses of early and late-chronic Toxoplasma gondii infection shows novel and stage specific transcripts

“…In addition, due to the isolation procedure, we are unable to say whether the identified host proteins were associated with the parasites or not, and we are not able to determine if any one protein is directly associated with the cyst wall. Nonetheless, it is interesting to note that the membrane associated host transporters TAP1 and TAP2 were identified in each sample by MS and are highly expressed in the brain during infection [10]. This may suggest that these proteins could be used by T. gondii to help transport components across the cyst wall.…”