Tim-3 is differently expressed in genetically susceptible C57BL/6 and resistant BALB/c mice during oral infection with Toxoplasma gondii

• Published in: European journal of microbiology & immunology 2013-09, Vol.3 (3), p.211-221
• Main Authors: Berrocal Almanza, L C, Muñoz, M, Kühl, A A, Kamradt, T, Heimesaat, M M, Liesenfeld, O
• Format: Article
• Language: English
• Subjects: Disease susceptibility; Gene expression; Genetic aspects; Health aspects; Microbiology and Immunology; Mouth diseases; Original; Toxoplasmosis
• ISSN: 2062-509X; 2062-8633
• DOI: 10.1556/EuJMI.3.2013.3.10

Tim-3 has opposing roles in innate and adaptive immunities. It not only dampens CD4+ and CD8+ T cells responses but also enhances the ability of macrophages to eliminate intracellular pathogens. After peroral infection with 100 cysts of Toxoplasma gondii genetically susceptible C57BL/6 mice develop an unchecked Th1 response associated with the development of small intestinal immunopathology. Here we report that upon infection with T. gondii, both susceptible C57BL/6 and resistant BALB/c mice exhibit increased frequencies of Tim-3+ cells in spleens and mesenteric lymph nodes. The number of Tim-3+ cells was significantly higher in C57BL/6 than in BALB/c mice. Tim-3 was expressed by macrophages, dendritic, natural killer, as well as CD4+ and CD8+ T cells. Highest frequencies of Tim-3+ cells were observed at the peak of Th1 responses (day 7 post infection) concurrent with the development of ileal immunopathology. Infected Tim-3-deficient BALB/c mice did not develop ileal immunopathology nor did their parasite loads differ from those in wildtype BALB/c mice. Thus, although Tim-3 is markedly upregulated upon infection and differentially regulated in susceptible and resistant mice upon infection with T. gondii, the absence of Tim-3 is not sufficient to overcome the genetic resistance of BALB/c mice to the development of Th1-driven small intestinal immunopathology.