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scenarios in DCs. Because DCs interact with all major lymphocyte types (B cells, T
cells and natural Killer cells) and because DCs have mutually exclusive functions
(antigen uptake compared to antigen presentation), it is perhaps not surprising that
different DC subsets/subtypes can be found. What is not clear, however, is whether
such subsets are the product of different ontogenesis with particular pathogen
recognition and effector functions (specialized lineage model) or if they represent
different functional states of a single lineage that itself can detect and respond
differently to distinct pathogens (functional plasticity model). Recent evidence
suggests that the simple ontogeny distinction of myeloid (derived from a common
myeloid progenitor cell) and lymphoid (derived from a common lymphoid
progenitor cell) DCs is not true.
DC subsets can be identified in the mouse and humans on the basis of the
expression of different cell surface markers (proteins and glycoproteins) (Shortman
and Liu 2002) in support of the specialized lineage model. Myeloid DCs (mDCs)
express the myeloid cell surface marker CD11c whereas plasmacytoid DCs (pDCs)
(proposed to be of the lymphoid lineage and so named because of their ultrastructural
resemblance to antibody-secreting plasma cells) express the CD45 isoform (B220)
normally expressed on B cells. Exposure of murine bone marrow pDCs to the mouse
virus lymphocytic choriomeningitis virus (LCMV), however, induced these pDCs to
differentiate into authentic mDCs by undergoing profound phenotypic and functional
changes, highlighting the functional plasticity of bone marrow pDCs (Zuniga,
McGavern, Pruneda-Paz, Teng, and Oldstone 2004).
The situation becomes more complicated with the evidence that pDCs can
develop efficiently from myeloid and lymphoid committed progenitors suggesting
the existence of a common DC progenitor (Shigematsu, Reizis, Iwasaki, Mizuno, Hu,
Traver, Leder, Sakaguchi, and Akashi 2004). In addition, hematopoietic cell lineage
commitment may not be an irreversible transition from progenitor to terminally
differentiated cell, as experiments show that enforced expression of the transcription
factor C/EBP
and/or in mature B cells efficiently re
phages (Xie, Ye, Feng, and Graf 2004). Complex cell ontogeny is certainly a feature of
the immune system. Lineage plasticity may also be a common but hidden feature of
α
programs them into macro-
β
hematopoietic cell types that are influential in the immune response, with the
extracellular signaling context maintaining an apparently fixed phenotypic steady
state, masking the capacity of changing to an alternative lineage phenotypic state if
different cellular input signals were supplied (Xie et al. 2004).
7.2.1.2 Toll-like Receptors
Regardless of whether DC subsets represent stages in a functional continuum or
distinct functional types, the problem of recognizing diverse pathogens remains. The
strategy of pattern recognition has evolved to deal with the problem of detecting
microbes in the context of microbial heterogeneity and rapid evolution. Pattern
recognition detects a limited set of conserved molecular patterns that are associated
with microbes, often called pathogen-associated molecular patterns (PAMPs). These
are recognized by pattern recognition receptors (PRRs) of which the Toll-like
receptor (TLR) family is the best characterized (Akira and Takeda 2004). DCs and
