Infection of dendritic cells by murine cytomegalovirus induces functional paralysis

Abstract

Cytomegalovirus (CMV), measles and HIV are the main human pathogens known to induce immunosuppression. Unlike measles and HIV, and despite the availability of a well studied animal model, little is known about the mechanisms that control CMV-induced immunosuppression. We hypothesized that dendritic cells (DCs), which are crucial in generating and maintaining immune responses, represent a target for CMV and that the transient, but profound, immunosuppression that accompanies CMV infection results from viral interference with DC functions. Here we show that DCs were permissive to murine CMV infection. In addition, DC infection prevented delivery of the signals required for T cell activation. Thus, CMV-mediated impairment of DC function may be crucial for virally induced immunosuppression and interleukin 2 is implicated as a key factor.

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Figure 1: MCMV infection of DCs in vitro and in vivo.
Figure 2: MCMV-infected DCs showed impaired antigen uptake.
Figure 3: MCMV infection altered the phenotype of immature D1 cells.
Figure 4: MCMV infection down-regulated expression of DC markers on DCs in vivo.
Figure 5: MCMV-infected DCs were refractile to phenotypic maturation after LPS stimulation.
Figure 6: DCs viability was not altered by MCMV infection.
Figure 7: MCMV infection altered the secretion of IL-12 and IL-2 by DCs.
Figure 8: MCMV infection of DCs impaired their allostimulatory capacity.

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Acknowledgements

We thank M. Wikstrom (The Lotteries Commission of Western Australia Flow Cytometry and Cell Sorting Facility) for assistance with the purification of DCs by cell sorting; H. Tabarias for help with the cytokine ELISA assays; and E. Maraskovsky, M. Smyth, G. Shellam, A Strasser, G. Begley, H. Farrell and A. Scalzo for continued support, critical discussions and reading of this manuscript. Supported by the National Health and Medical Research Council of Australia (grants 110287, 110288), a Wellcome Trust Overseas Senior Research Fellowship in Biomedical Science in Australia (M. A. D.-E.) and AMRAD (D. M. A.).

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Correspondence to Mariapia A. Degli-Esposti.

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Andrews, D., Andoniou, C., Granucci, F. et al. Infection of dendritic cells by murine cytomegalovirus induces functional paralysis. Nat Immunol 2, 1077–1084 (2001). https://doi.org/10.1038/ni724

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