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Journal of Virology, October 2003, p. 10943-10956, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.10943-10956.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus Inhibits Differentiation of Monocytes into Dendritic Cells with the Consequence of Depressed Immunological Functions

Sara Gredmark and Cecilia Söderberg-Nauclér*

Karolinska Institutet, Stockholm, Sweden

Received 19 February 2003/ Accepted 10 July 2003

Human cytomegalovirus (HCMV) infections in immunocompromised patients are associated with impaired immunological functions. Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity and are believed to carry latent HCMV. We demonstrate here that HCMV infection of monocytes results in a block in the cytokine-induced differentiation of monocytes into functionally active CD1a-positive dendritic cells, which exhibited severely depressed immunological functions in vitro. The HCMV-infected cells exhibited a significantly reduced ability to endocytose fluorescein isothiocyanate-labeled dextran particles as well as a more than 90% reduced ability to migrate in response to the chemoattractant factors RANTES, MIP-1{alpha}, and MIP-3ß. Interestingly, HCMV-infected cells expressed high levels of the costimulatory molecule CD86, in contrast to the low levels of expression that was observed on uninfected monocytes and uninfected immature dendritic cells. Furthermore, HCMV-infected CD1a-negative cells were unable to induce a T-cell response. Thus, these observations suggest that HCMV infection of monocytes in vitro blocks cytokine-induced dendritic cell differentiation, and since dendritic cells play a central role in initiating immune responses, these findings suggest a powerful tactic to avoid immune recognition and to blunt the immune response at early phases of infection.

* Corresponding author. Mailing address: Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. Phone: 46 8 517 79896. Fax: 46 8 517 79896. E-mail: cecilia.soderberg.naucler{at}cmm.ki.se.

Journal of Virology, October 2003, p. 10943-10956, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.10943-10956.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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