Modulating TH1/TH2 responses with microbes, dendritic cells, and pathogen recognition receptors

The adaptive immune system has evolved different types of immune responses, each one effective against a given class of pathogen. For example, Th1 and Th2 responses represent two qualitatively different types of immune responses that are preferentially effective against intracellular microbes and helminths, respectively. Since the original description of Th1 and Th2 T-cell clones (1), we have learned much about the cytokines that influence the type of Th response. Thus, interleukin-4 (IL-4) is known to induce IL-4 production in T cells; conversely IL-12 and interferon-gamma (IFN-gamma) are known to induce IFN-gamma production by T cells. However, the original sources of these cytokines in vivo are less clear. Recent developments from several labs point to a potential role for dendritic cells (DCs) in orchestrating this decision making process. Here, we present our current view of DC development, and then review the evidence for two opposing concepts: (1) that distinct subsets of DCs are predetermined to differentially bias the T-helper response; and (2) that microbes and the local microenvironment are potent modulators of DC function. Thus, nature appears to have evolved different mechanisms to regulate immune responses via DCs.