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  • 1 Department of Microbiology and Hygiene, Charité, University Medicine Berlin, Berlin, Germany
  • 2 Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité, University Medicine Berlin, Berlin, Germany
  • 3 German Rheumatism Research Center (DRFZ), A Leibniz Institute, Berlin, Germany
  • 4 Department of Gastroenterology, Infectology and Rheumatology / Research Center ImmunoSciences (RCIS), Charité, University Medicine Berlin, Berlin, Germany
  • 5 Institute for Immunology, Jena University Hospital, Jena, Germany
  • 6 Roche Molecular Systems, Pleasanton, CA, USA
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Abstract

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.

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