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7.3 Gene Expression Programs in Antigen-Presenting Cells
Antigen presenting cells (APCs) must exhibit considerable functional plasticity to
initiate the complex series of events that leads to these different adaptive immune
responses being appropriate to the initial antigenic trigger. APCs have therefore been
the subject of considerable interest in determining global gene expression programs
using postgenomic tools such as DNA microarrays.
7.3.1 Common Transcriptional Reprogramming
of Dendritic Cells by Pathogens
Before antigen encounter, it seems that APCs that are similar in ontogeny (such as
macrophages and immature monocyte-derived DCs) are similar in gene expression
profile, sharing 96% of their expressed gene networks (Chaussabel, Semnani,
McDowell, Sacks, Sher, and Nutman 2003). Following exposure to the same
pathogen the two cell types respond quite differently at the transcriptional level, with
only 40% of the regulated genes being shared by both (Chaussabel et al. 2003). This
is perhaps not too surprising as macrophages and DCs have different roles in the
immune response. Macrophages and monocytes mainly sustain and control the local
inflammatory process as well as phagocytosing and destroying microbes. The
distinct functional roles of DCs, participating in the inflammatory process at the site
of infection, while being able to transit to local lymphoid tissue to prime T cells,
suggest a number of different functional and therefore transcriptional states for DCs.
Time course studies of murine and human DCs exposed to whole pathogens
and PAMPs such as lipopolysaccharide (LPS) and double-stranded RNA (dsRNA),
show DCs have at least three distinct transcriptional states (Huang, Liu, Majewski,
Schulte, Korn, Young, Lander, and Hacohen 2001; Granucci, Vizzardelli, Virzi,
Rescigno, and Ricciardi-Castagnoli 2001a; Granucci, Vizzardelli, Pavelka, Feau,
Persico, Virzi, Rescigno, Moro, and Ricciardi-Castagnoli 2001b; Kwan & Kellam,
unpublished observations). These “core” transcriptional responses occur independent
of the type of antigen and reflect the essential functions of a maturing DC (Fig. 2).
Fig. 2.
Gene expression programs at different transcriptional stages of dendritic cell
maturation. The solid and dashed lines represent transient and sustained upregulation of
different functional groups of genes.
