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Antimicrobial effects of murine mesenchymal stromal cells directed against Toxoplasma gondii and Neospora caninum: role of immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs) |
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| Authors: | K. Spekker M. Leineweber D. Degrandi V. Ince S. Brunder S. K. Schmidt S. Stuhlsatz J. C. Howard G. Schares Ö. Degistirici R. Meisel R. V. Sorg J. Seissler A. Hemphill K. Pfeffer W. Däubener |
| Affiliation: | 1. Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, Universit?tsstrasse 1 Geb. 22.21, 40225, Düsseldorf, Germany 2. Institute for Genetics, University of K?ln, Cologne, Germany 3. Federal Research Institute for Animal Health, Institute of Epidemiology, Friedrich-Loeffler-Institute, Wusterhausen, Germany 4. Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University, Düsseldorf, Germany 5. Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, Düsseldorf, Germany 6. Medical Clinic Innenstadt, Ludwig-Maximilians-University, Munich, Germany 7. Institute of Parasitology, University of Bern, Bern, Switzerland |
| Abstract: | Mesenchymal stromal cells (MSCs) have a multilineage differentiation potential and provide immunosuppressive and antimicrobial functions. Murine as well as human MSCs restrict the proliferation of T cells. However, species-specific differences in the underlying molecular mechanisms have been described. Here, we analyzed the antiparasitic effector mechanisms active in murine MSCs. Murine MSCs, in contrast to human MSCs, could not restrict the growth of a highly virulent strain of Toxoplasma gondii (BK) after stimulation with IFN-γ. However, the growth of a type II strain of T. gondii (ME49) was strongly inhibited by IFN-γ-activated murine MSCs. Immunity-related GTPases (IRGs) as well as guanylate-binding proteins (GBPs) contributed to this antiparasitic effect. Further analysis showed that IFN-γ-activated mMSCs also inhibit the growth of Neospora caninum, a parasite belonging to the apicomplexan group as well. Detailed studies with murine IFN-γ-activated MSC indicated an involvement in IRGs like Irga6, Irgb6 and Irgd in the inhibition of N. caninum. Additional data showed that, furthermore, GBPs like mGBP1 and mGBP2 could have played a role in the anti-N. caninum effect of murine MSCs. These data underline that MSCs, in addition to their regenerative and immunosuppressive activity, function as antiparasitic effector cells as well. However, IRGs are not present in the human genome, indicating a species-specific difference in anti-T. gondii and anti-N. caninum effect between human and murine MSCs. |
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