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

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.

Neospora caninum infection induces an isolate virulence-dependent pro-inflammatory gene expression profile in bovine monocyte-derived macrophages

“…In the present study, NLRs related to inflammasome formation [39] NAIP, NOD2, NLRC4 and NLRP12 were only over-expressed in cells infected with live tachyzoites of both isolates, suggesting different recognition and thus subsequent responses induced by live and HK tachyzoites, likely because NLRs act as intracellular surveillance molecules. The involvement of all these receptors in T. gondii sensing has been reported previously [50][51][52], and here the results suggest for the first time that they may be involved in the bovine MØ inflammatory response against neosporosis.…”

Molecular Alterations in the Stomach of Tff1-Deficient Mice: Early Steps in Antral Carcinogenesis

“…Furthermore, a role for Tff1 as a scavenger for ROS/RNS could also be the reason why Tff1 is ectopically expressed during various inflammatory conditions in mice, such as encephalitis, asthma, pancreatitis, and in the murine spleen after Toxoplasma gondii infection [39,[56][57][58]. Here, the reactive thiol of Tff1 could protect the tissue from damage by the oxidative burst.…”

“…The specific primer pairs used in this RT-PCR study have been published previously (Epdr1, MB1890/1891; Fcgbp, MB1516/1517; Gkn3, MB2656/2657; Tff1, MD7/MD8; Tff3, MB1847/MB1848; [56,58,80]) or are listed in Table 1 (Actb, Agr2, Cckbr. Cxcl1, Cxcl5, Gast, Gkn1, Gkn2, Irx3, Mist1/Bhlha15, Muc5ac, Muc6, Pdia3, Pdx1, Tff2, Troy/Tnfrsf19).…”

The Tumor Suppressor TFF1 Occurs in Different Forms and Interacts with Multiple Partners in the Human Gastric Mucus Barrier: Indications for Diverse Protective Functions

“…This might be the reason why TFF1 is ectopically expressed during inflammatory processes in humans as well as in animal models. Typical examples are duodenal ulcers, Crohn's disease, pancreatitis, asthma, encephalitis, and in the murine spleen after Toxoplasma gondii infection [8,9,[66][67][68][69].…”