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

Eva Znalesniak,Ulrike Händel,Franz Salm,Ting Fu,Werner Hoffmann

doi:10.3390/ijms18061245

Abstract

The spleen plays an important role in coordinating both adaptive and innate immune responses. Here, the transcriptional response to T. gondii infection in the murine spleen was characterized concerning inflammasome sensors (two different models: seven days after oral or four weeks after intraperitoneal infection). Additionally, Tff1KO and Tff3KO mice were investigated because TFF genes are often upregulated during inflammation. The expression of the pattern-recognition receptors Nlrp3, Nlrp12, and Nlrp1a was significantly increased after infection. This increase was diminished in Tff1KO and Tff3KO mice pointing towards a positive regulation of the inflammatory response by Tff1 and Tff3. Furthermore, the transcription of Tff1 (encoding a motogenic lectin) and other secretory genes was analyzed, i.e., gastrokines (Gkn), IgG Fc binding protein (Fcgbp), and the mucin Muc2. The corresponding gene products belong to an interactome protecting mucous epithelia. Tff1 was significantly induced after infection, which might increase the motility of immune cells. In contrast, Gkn3, Fcgbp, and Muc2 were downregulated seven days after oral infection; whereas four weeks after i.p. infection only Gkn3 remained downregulated. This might be an indication that Gkn3, Fcgbp, and Muc2 are involved in the transient disruption of the splenic architecture and its reorganization, which is characteristic after T. gondii infection.

Highlights

The spleen is the largest secondary lymphoid organ of the body with various functions, the immune function being the most important one [1,2]
Gkn3, Fcgbp, and Muc2 were downregulated seven days after oral infection; whereas four weeks after i.p. infection only Gkn3 remained downregulated. This might be an indication that Gkn3, Fcgbp, and Muc2 are involved in the transient disruption of the splenic architecture and its reorganization, which is characteristic after T. gondii infection
We investigated the spleen of Tff1KO mice after i.p

Summary

Introduction

The spleen is the largest secondary lymphoid organ of the body with various functions, the immune function being the most important one [1,2]. Phagocytosis, T cell-mediated immunity, and B cell-mediated humoral immunity occur mainly in the white pulp and the marginal zone of the spleen. The red pulp of the spleen is a major blood filter, is involved in phagocytosis, and is a key site for iron metabolism; the latter being a prerequisite for the oxidizing function of monocytes. The spleen is 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]. 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 spleen participates in metabolic and immunological abnormalities described in obesity, and splenectomy attenuates the progression of obesity and decreases insulin hypersecretion [9]

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Conclusion