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Cellular distribution of CD200 receptor in rats and its interaction with cytomegalovirus e127 protein

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Abstract

CD200 is a membrane protein that interacts with CD200R on the surface of immune cells and delivers an inhibitory signal. In this study, we characterized the distribution of inhibitory CD200R in rats. In addition, we investigated if e127, a homologue of rat CD200 expressed by rat cytomegalovirus (RCMV), can suppress immune functions in vitro. RT-PCR analysis was carried out to test the expression of CD200R in different rat tissues and flow cytometry was performed to characterize CD200R at the cellular level. To test the inhibitory functions of e127, a co-culture system was utilized in which immune cells were incubated with e127-expressing cells. The strongest CD200R expression was detected in lymphoid organs such as bone marrow and spleen. Flow cytometry analyses showed that CD200R+ cells were mainly CD4− dendritic cells (DC) and CD4+ T cells in the spleen. In blood, nearly all monocytes and granulocytes expressed CD200R and in bone marrow the NKRP1low subset of natural killer cells highly expressed CD200R. In addition, both peritoneal macrophages and the NR8383 macrophage cell line carried CD200R. At the functional level, viral e127 conferred an inhibitory signal on TNFα and IL6 cytokine release from IFNγ-stimulated macrophages. However, e127 did not affect the cytotoxic activity of DC. CD200R in the rat is mainly expressed on myeloid cells but also on non-myeloid cell subsets, and RCMV e127 can deliver inhibitory signals to immune cells by engaging CD200R. The RCMV model provides a useful tool to study potential immune evasion mechanisms of the herpesviridae and opens new avenues for understanding and controlling herpesvirus infections.

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Funding

Mohamed A. El-Mokhtar was kindly supported by the GERLS (German Egyptian Research Long-Term Scholarships) program from the German Academic Exchange Service (DAAD).

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  1. Mohamed A. El-Mokhtar

    Present address: Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt

Authors and Affiliations

  1. Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany

    Mohamed A. El-Mokhtar, Agnieszka Bauer, Julia Madela & Sebastian Voigt

  2. Department of Pediatric Oncology/Hematology/SCT, Charité-Universitätsmedizin, Berlin, Germany

    Sebastian Voigt

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The rats were kept under specific pathogen-free conditions with ad libitum diet at the animal facility of the Robert Koch Institute. All procedures performed involving animals were in accordance with the ethical standards of the Robert Koch Institute, Berlin, Germany, and were approved by the ethics committee of Berlin state authorities.

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El-Mokhtar, M.A., Bauer, A., Madela, J. et al. Cellular distribution of CD200 receptor in rats and its interaction with cytomegalovirus e127 protein. Med Microbiol Immunol 207, 307–318 (2018). https://doi.org/10.1007/s00430-018-0552-3

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