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. 2021:28:13.
doi: 10.1051/parasite/2021010. Epub 2021 Feb 25.

Expression of TIGIT in splenic and circulatory T cells from mice acutely infected with Toxoplasma gondii

Shuai Wang  1 , Haoran Li  1 , Fuqiang Zhang  1 , Yuankai Jiao  2 , Qing Xie  1 , Zhenchao Zhang  1 , Xiangrui Li  3
Affiliations

Expression of TIGIT in splenic and circulatory T cells from mice acutely infected with Toxoplasma gondii

Shuai Wang et al. Parasite. 2021.

Abstract
in English, French

The surface protein TIGIT (T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain) has been characterized as an important regulator of cell-mediated immune responses in various infections. However, TIGIT expression in immune cells of mice infected with Toxoplasma gondii has not been investigated. Here, we detected TIGIT expression and related phenotypes by flow cytometry and real-time PCR in splenic and circulatory T cells of mice infected with the T. gondii RH strain. We found that the expression of TIGIT on the surface of CD4+ T cells and CD8+ T cells from the spleen and peripheral blood mononuclear cells decreased in the early stage, but increased significantly in the late stage of acute T. gondii infection in mice. Importantly, TIGIT expression was positively correlated with lesions in the murine spleen. In addition, T. gondii-specific TIGIT+TCM cells in the spleen were activated and transformed into TIGIT+ TEM cells. Hematoxylin and eosin staining of spleen sections and real-time PCR showed that the severity of splenic lesions was positively correlated with the T. gondii load. This study demonstrates that acute T. gondii infection can regulate the expression of TIGIT in T cells and affect immune cell function.

Title: Expression de TIGIT dans les cellules T spléniques et circulatoires de souris lourdement infectées par Toxoplasma gondii.

Abstract: La protéine de surface TIGIT a été caractérisée comme un régulateur important des réponses immunitaires à médiation cellulaire dans diverses infections. Cependant, l’expression de TIGIT dans les cellules immunitaires de souris infectées par Toxoplasma gondii n’a pas été étudiée. Ici, nous avons détecté l’expression de TIGIT et les phénotypes associés par cytométrie en flux et PCR en temps réel dans les cellules T spléniques et circulatoires de souris infectées par la souche RH de T. gondii. Nous avons constaté que l’expression de TIGIT à la surface des cellules T CD4 + et des cellules T CD8 + de la rate et des cellules mononucléées du sang périphérique diminuait au stade précoce, mais augmentait de manière significative au stade avancé de l’infection aiguë à T. gondii chez la souris. Surtout, l’expression de TIGIT était positivement corrélée avec les lésions de la rate de la souris. De plus, des cellules TIGIT+TCM spécifiques de T. gondii dans la rate ont été activées et transformées en cellules TEM. La coloration à l’hématoxyline et à l’éosine (H&E) des coupes de rate et la PCR en temps réel ont montré que la gravité des lésions spléniques était positivement corrélée à la charge en T. gondii. Cette étude démontre qu’une infection aiguë par T. gondii peut réguler à la hausse l’expression de TIGIT dans les cellules T et affecter la fonction des cellules immunitaires.

Keywords: CD226; T cells; TIGIT; Toxoplasma gondii.

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Figures

Fig. 1
Fig. 1
Changes in TIGIT expression on T cells in different tissues after T. gondii infection. (A) Proportions of TIGIT+ cells among CD4+ and CD8+ T cells in T. gondii-infected (RH) and normal mice (Nc) at 7 days after infection. (B) Results of statistical analysis of the percentage of TIGIT+ cells among CD4+T and CD8+T cells in RH and Nc mice at 7 days after infection. (C) Dynamic changes in the percentages of TIGIT+ in T cells at different time points. The results are representative of three independent experiments with five mice in each group per experiment, with data denoting means ± SDs.
Fig. 2
Fig. 2
Changes in CD226 expression on T cells in different tissues after T. gondii infection. (A) Proportions of CD226+ cells among CD4+T and CD8+T cells in T. gondii-infected (RH) and normal mice (Nc) at 7 days after infection. (B) Results of statistical analysis of the percentage of CD226+ cells among CD4+T and CD8+T in RH and Nc mice at 7 days after infection. (C) Dynamic changes in the percentages of CD226+ T cells at different time points. The results are representative of three independent experiments with five mice in each group per experiment, with data denoting means ± SDs.
Fig. 3
Fig. 3
Relative contributions of memory T cell subsets of TIGIT+ T cells after T. gondii infection. (A) Dynamic changes in memory T cell subsets of TIGIT+ T cell in PBMCs at different time points following RH infection. (B) Dynamic changes in memory T cell subsets of TIGIT+T cells in the spleen at different time points following RH infection. The results are representative of three independent experiments with five mice in each group per experiment, with data denoting means ± SDs.
Fig. 4
Fig. 4
Dynamic pathological changes in the spleen during acute T. gondii infection. (A) Relative expression of TgSAG1 at 0, 1, 3, 5, and 7 days post infection in the PBMCs and spleen. (B) Spleen index values of the RH and Nc groups. The results are representative of three independent experiments with five mice per group per experiment; with data denoting means ± SDs; (C) H&E staining of spleen sections at different time points in the RH infection group. The original magnification was 100×, and the corresponding images on the right were magnified at 400×.
Fig. 5
Fig. 5
mRNA expression of TIGIT and CD226 in the PBMCs and spleens from mice infected with the T. gondii RH strain, as assessed by qRT-PCR. A: Data obtained from PBMCs. B: Data obtained from the spleen. Values are the means from triplicate measurements, with data denoting means ± SDs; three independent experiments were performed with five mice per group. *p < 0.05, **p < 0.01 and ***p < 0.001 (compared to the control).
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