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Published online before print February 24, 2006

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(Journal of Leukocyte Biology. 2006;79:932-940.)
© 2006 by Society for Leukocyte Biology

Dendritic cell function in cytomegalovirus-infected patients with mononucleosis

Giada Frascaroli^*,, Stefania Varani^*,, Antonio Mastroianni, Sven Britton^¶, Davide Gibellini^*, Giada Rossini^*, Maria P. Landini^* and Cecilia Söderberg-Nauclér^,1

Center for Molecular Medicine and
^¶ Unit of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;
^* Department of Clinical and Experimental Medicine, Section of Microbiology, University of Bologna, Italy;
Department of Virology, University of Ulm, Germany; and
Unit of Infectious Diseases, "G.B. Morgagni" General Hospital, Forlì, Italy

¹Correspondence: Karolinska Institutet, Center for Molecular Medicine, L8:03, Karolinska Hospital, SE-171 76 Stockholm, Sweden. E-mail: cecilia.soderberg.naucler{at}cmm.ki.se

ABSTRACT

Dendritic cells (DCs) are important target cells for human cytomegalovirus (HCMV) infection, and the virus has been shown to hamper the differentiation and maturation pathways of these cells in vitro. In the present study, we examined the function of monocyte-derived DCs obtained from immunocompetent individuals undergoing symptomatic HCMV infection in terms of immunophenotypic characteristics, pinocytosis, lymphocyte stimulation capacity, and cyto-chemokine secretion in comparison with DCs obtained from healthy controls. Immature and lipopolysaccharide (LPS)-stimulated DCs obtained from patients actively infected with HCMV expressed significantly lower levels of major histocompatibility complex (MHC) class II molecules. The inhibition of expression of MHC class II molecules by HCMV appeared to be functionally relevant, as mature DCs obtained from patients with HCMV mononucleosis were inefficient in stimulating proliferation of allogenic lymphocytes. Finally, the pattern of cyto-chemokines secreted by DCs obtained from patients with HCMV mononucleosis was characterized by a proinflammatory profile with an increased production of interleukin (IL)-1ß, tumor necrosis factor , CC chemokine ligand 2 (CCL2) and CCL3, and reduced secretion of IL-10 upon LPS stimulation. During symptomatic HCMV infection in the immunocompetent host, DCs exhibit an impaired immunophenotype and function. These effects may contribute to the viral-induced immunomodulation, which is often observed in HCMV-infected patients.

Key Words: viral infection • antigen-presenting cells • viral-induced immunomodulation

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