Transcriptomic analysis of global changes in cytokine expression in mouse spleens following acute Toxoplasma gondii infection

Abstract

Toxoplasma gondii is a global pathogen that infects a wide range of animals and humans. During T. gondii infection, the spleen plays an important role in coordinating the adaptive and innate immune responses. However, there is little information regarding the changes in global gene expression within the spleen following T. gondii infection. To address this gap in knowledge, we examined the transcriptome of the mouse spleen following T. gondii infection. We observed differential expression of 2310 transcripts under these conditions. Analysis of KEGG and GO enrichment indicated that T. gondii alters multiple immune signaling cascades. Most of differentially expressed GO terms and pathways were downregulated, while immune-related GO terms and pathways were upregulated with response to T. gondii infection in mouse spleen. Most cytokines were upregulated in infected spleens, and all differentially expressed chemokines were upregulated which enhanced the immune cells chemotaxis to promote recruitment of immune cells, such as neutrophils, eosinophils, monocytes, dendritic cells, macrophages, NK cells, basophils, B cells, and T cells. Although IFN-γ-induced IDO (Ido1) was upregulated in the present study, it may not contribute a lot to the control of T. gondii because most differentially expressed genes involved in tryptophan metabolism pathway were downregulated. Innate immunity pathways, including cytosolic nucleic acid sensing pathway and C-type lectins-Syk-Card9 signaling pathways, were upregulated. We believe our study is the first comprehensive attempt to define the host transcriptional response to T. gondii infection in the mouse spleen.

Transcriptional Responses in the Murine Spleen after Toxoplasma gondii Infection: Inflammasome and Mucus-Associated Genes

“…The spleen is also a rich source for endocrine secretions, e.g., it is a key player in the “cytokine storm” that develops after infection and trauma [3,4]. For example, tumor necrosis factor (TNF)-α is produced in the spleen in high amounts and individuals having undergone splenectomy are highly susceptible to infections [5,6].…”

“…The host immune system plays a critical role in the response to T. gondii infection [11,12,13]. Immune factors involved in controlling T. gondii infection are, e.g., interleukin (IL)-6, IL-10, IL-12, IL-33, and interferon (IFN)-γ [4]. In humans, infections are normally subclinical and severe complications occur in immunocompromised patients and because of congenital infection.…”

“…Recently, cytokine expression in the murine spleen has been investigated after intraperitoneal (i.p.) or oral T. gondii infection [4,14]. Of note, all the differentially expressed chemokines were upregulated; whereas most of the differentially expressed chemokine receptors were downregulated [4].…”

“…or oral T. gondii infection [4,14]. Of note, all the differentially expressed chemokines were upregulated; whereas most of the differentially expressed chemokine receptors were downregulated [4]. Furthermore, T. gondii infection caused a changed miRNA regulation network in mouse spleen as well as transcriptional changes of splenocyte organelle components [15,16].…”

Molecular characterization and diagnostic potential of serine proteinase inhibitors from Taenia solium

“…The sera against Toxoplasma gondii were obtained from six pigs that were inoculated peritoneally with 1000 oocysts. T. gondii infection was confirmed by polymerase chain reaction (PCR) as described previously (He et al 2016) at 15 dpi.…”