TFF Peptides Play a Role in the Immune Response Following Oral Infection of Mice with Toxoplasma gondii

Abstract

The peptide trefoil factor family 3 (TFF3) is a major constituent of the intestinal mucus, playing an important role in the repair of epithelial surfaces. To further understand the role of TFF3 in the protection of intestinal epithelium, we tested the influence of TFF3 in a murine Toxoplasma gondii-induced ileitis model. Surprisingly, TFF3KO mice showed a reduced immune response in the ileum when compared to wild-type animals. Interleukin-12 and interferon-γ expression levels as well as the number of CD4+ lymphocytes were reduced in the infected TFF3KO mice. These effects were in line with the trend of elevated parasite levels in the ileum. Moreover, TFF1 expression was upregulated in the spleen of infected mice. These initial results indicate that TFF3 is involved in the immune pathology of T. gondii infection-induced intestinal inflammation. Thus far, the mechanisms of how TFF3 influences the immune response are not fully understood. Further studies should identify if TFF3 affects mucus sensing of dendritic cells and how TFF3 is involved in regulating the immune response as an intrinsic secretory peptide of immune cells.

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

“…In the spleen, particularly TFF2 and TFF3 are expressed [14,22,46,47]. The biosynthesis of TFF1 and TFF3 is complex; both are secretory peptides containing an odd number of cysteine residues and are able to form disulfide-linked heterodimers with GKN2 and FCGBP, respectively [48,49,50].…”

“…The specific primer pairs used in this RT-PCR study have been also published previously ( Actb , MB1912/MB1913; Ifnγ , MB2054/MB2055; Il1β , MB2038/MB2039; Tff1 , MD7/MD8; Nlrp1a , MB2576/MB2577; Nlrp3 , MB2584/MB2585; Nlrc4 , MB2382/MB2383; Nlrc5 , MB2608/MB2609; Mnda , MB2600/MB2601; [14,17]) or are listed in Table 1 ( Fcgbp , Gkn3 , Muc2 , Nlrp12 , Toll-like receptor/ Tlr4 ).…”

Protein profiling of nasopharyngeal aspirates of hospitalized and outpatients revealed cytokines associated with severe influenza A(H1N1)pdm09 virus infections: A pilot study

“…Its function is not defined, but it may protect the mucosa from injury, stabilize the mucus layer, and affect healing of the epithelium. It also plays a role in the immune response following infection with Toxoplasma gondii [45]. In addition, it downregulates IL-8 and IL-6 levels [46].…”

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

“…Genotyping of Tff1 KO mice has been reported in detail previously [80]. The primer pairs used for PCR analysis have been reported [56].…”

“…The primer pairs used for PCR analysis have been reported [56]. Isolation and purification of total gastric RNA (using TRIzol TM Reagent; ambion by life technologies, Carlsbad/CA, USA) as well as RT-PCR analysis (reverse transcriptase: Takara Bio Europe, Saint Germain en Laye, France) and semi-quantitative evaluation of the relative expression levels of selected genes including statistical analysis was as described in detail previously [80]. Relative intensities were normalized against the corresponding relative β-actin intensities.…”