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other cell types such as epithelial cells and B cells express a range of the ten known
human TLRs. In addition, DC subsets express different combinations of TLRs (Table 1).
This implies a given DC population or subset will only respond to the pathogens for
which they have the appropriate TLRs.
.
Table 1.
TLRs expressed on human dendritic cells (adapted from Iwasaki and Medzhitov 2004)
Monocytes
1
mDCs
2
pDCs
3
In vitro
differenti-
ated DCs
4
TLR1
+
+
+
+
TLR2
+
+
−
+
TLR3
−
+
−
+
TLR4
+
+
−
+
TLR5
+
+
−
+/
−
TLR6
+
+
+
+
5
TLR7
+/
−
+/
−
+
−
TLR8
+
+
−
+
TLR9
−
−
+
−
TLR10
−
+
+
?
1
human CD14 positive monocytes.
2
human myeloid dendritic cells.
3
human plasmacytoid dendritic cells.
4
Dendritic cells generated
in vitro
from CD14
+
monocytes by culture in the presence of
GM-CSF and IL4.
5
+/
−
indicates that the results of different studies do not concur.
TLRs differ in their ligand specificity and the signal transduction pathways they
activate, thereby triggering antimicrobial and inflammatory responses and DC
maturation. This comprises both conserved signaling pathways such as MyD88-
dependent activation of the NFkB pathway, and receptor-specific signaling such as
the MyD88-independent activation of the IRF3 transcription factor by TLR4
(Iwasaki and Medzhitov 2004). How these signals combine to influence the various
facets of DC function is not known in detail. However, it is reasonable to assume that
the pathogen recognition and receptor signaling logic must influence the
transcriptional state of the DC and is therefore crucial for DC function.
7.2.2 Differential Outcomes; T
H
1, T
H
2, and Tolerogenic T-cell Responses
DCs are essential for activation and differentiation of naive T cells into T helper type
1 (T
H
1) cells, T helper type 2 (T
H
2) cells, and cytotoxic T lymphocytes. They are
also important for stimulating mature B cells to become antibody-producing plasma
cells in the absence of T-cell help (Jego, Palucka, Blanck, Chalouni, Pascual, and
Banchereau 2003; Poeck, Wagner, Battiany, Rothenfusser, Wellisch, Hornung,
Jahrsdorfer, Giese, Endres, and Hartmann 2004), and for inducing peripheral
tolerance to self antigens. These processes, however, normally occur in secondary
lymphoid organs. Therefore, following antigen exposure DCs must migrate to local
lymphoid organs where they can interact with T and B cells. This involves functional
reprogramming of DCs including the upregulation of costimulatory and MHC
