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maturation stimulus, and with maturation DCs downmodulate their endocytic
activity and upregulate peptide processing and presentation. Upon maturation, they
become mobile and are led by their homing receptors toward lymphatic tissues.
Interestingly, immature Langerhans type DCs, which reside in epidermal and
mucosal tissues, only become highly susceptible after maturation (Hertel et al.
2003; Reeves et al. 2005), whereas immature interstitial type DCs can be readily
infected by HCMV (Riegler et al. 2000; Moutaftsi et al. 2002). It is tempting to
speculate that HCMV is endocytosed by immature DCs in mucosal tissues, thus
providing a maturation stimulus, which then leads to migration toward the draining
lymph node and renders the cells permissive to HCMV replication. In the lymph
node, productively infected mature DCs may spread the virus to other cells, whereas
their immune-stimulatory capacity may be restricted. To further temper an antiviral
immune response, infected mature DCs may directly and indirectly inhibit T cell
functions (Raftery et al. 2001). However, despite such immunosuppressive effects,
immunocompetent hosts regularly develop a strong T cell response protecting from
clinical manifestations of the infection. Cross-presentation of viral antigens by
DCs following uptake of apoptotic material from infected cells has been described
as an explanation for the well-known robust immune response to HCMV in the
normal host (Tabi et al. 2001).
Fibroblasts
Fibroblasts are not only the standard cell culture system for propagation of
HCMV to high titers (Mocarski et al. 2006), but they are also among the major
targets of HCMV in vivo (Sinzger et al. 1995). Efficient replication in such a
ubiquitous cell type opens the possibility for HCMV to replicate in virtually every
organ. Consequently, infected connective tissue cells are assumed to contribute to
efficient spread of HCMV in organs as different as adrenal glands, bone marrow,
heart, kidney, liver, lung, pancreas, placenta, small bowel and spleen (Bissinger
et al. 2002). If the particular property of cultured fibroblast to generate and release
high titers of viral progeny also applies for infected connective tissue cells in vivo,
then they might contribute greatly to the highly dynamic proliferation of HCMV
during acute infections (Emery et al. 1999).
Smooth Muscle Cells
Like fibroblasts, smooth muscle cells are also ubiquitously distributed
throughout the body. Their basic function is generation of kinetic force by
contraction of the actin-myosin skeleton, which may be controlled either by
the autonomic nervous system, hormones or stimuli from neighboring cells.
Given their spatial organization as multicellular layers in the wall of hollow
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