Response of intestinal DCs to infection. (a) In the steady state, DCs resident in the intestine are conditioned by epithelial cell derived factors and promote the differentiation of Foxp3+ Treg and IgA secreting B cells upon migration to the MLN. This may occur following sampling of the commensal flora or in response to self-antigens derived from the intestinal epithelium. A small number of DC may also be recruited that escape conditioning and drive Th1 or Th17 responses. These DC may share a precursor with other DC resident in the intestine in the steady state, but encounter bacterial products or other stimuli before conditioning can take place, or they may derive from distinct precursors and be refractory to conditioning. These cells could act as sentinels for the presence of pathogenic species, or mount responses aimed at controlling the commensal flora. (b) In contrast to the commensal flora, some pathogenic species possess virulence factors that allow them to invade the intestinal epithelium and subvert immune responses to enhance their replication. Invasion of the epithelium leads to activation of cytosolic PRR and enhanced production of chemokines and pro-inflammatory cytokines. Neutrophils, macrophages and DC precursors are recruited to the site and become activated by a combination of signals from pathogens and pro-inflammatory cytokines and chemokines. Whether these DC precursors are shared with populations of DC present in the steady state remains unclear. Although DCs resident in the tissues prior to infection may not take on pro-inflammatory function, it is possible that their ability to promote regulatory T cell differentiation may be impeded. Pathogenic microbes may also reach CD103− DC resident in the LN which are capable of driving Th1 responses, likely as a result of not being conditioned in the intestine.