The same research group [2] further examined the fate of latex microspheres injected into the skin and noticed that by 18 h after injection most microspheres were phagocytosed. Of note, a large population of cells containing FITC-latex accumulated in the draining lymph nodes (LNs), mainly in the T-cell area. These cells phenotypically resembled DCs and were absent from monocyte-deficient op/op mice. These observations suggested that

a subset of monocyte-derived DCs could play a major role in buy STA-9090 presentation of particulate antigens and were reminiscent of old studies showing that DCs could be obtained in culture from human PBMCs [3, 4]. Although the precursors were not formally identified, they were plentiful in human blood and adherent, suggesting a monocytic lineage. More recently, Geissmann and colleagues [5] examined blood monocytes in mice and humans and identified two functional subsets as defined by the level of expression of CX3CR1. Resident CX3CR1high monocytes were found in the blood and noninflamed peripheral organs where they homed in a CX3CR1-dependent way. CX3CR1low monocytes were short-lived, were actively recruited to inflamed tissues independently of their CX3CR1 genotype, and differentiated into functional DCs that had the ability to stimulate naive T cells. Although the authors proposed

the term “inflammatory monocytes” for the immediate precursors Interleukin-3 receptor of antigen-presenting DCs, we will name them “inflammatory DCs,” unless discussing monocyte differentiation to DCs, as subsequent reports clearly indicate that most “inflammatory monocytes” GSK126 differentiate into CD11c+ cells displaying functional properties of the dendritic family. Other identified inflammatory monocytes such as Ly6Chigh or CCR2+ monocytes are discussed later in this review in the sections Th2-type immunity and Th1-type immunity. These observations

identified a novel population of DCs, which do not derive from a MDP (macrophage/DC precursor)/CDP (common DC progenitor) as shown for so-called classical DCs such as conventional and plasmacytoid DCs, but rather from monocytes in inflammatory conditions (Fig. 1). This raises the question of the respective role of conventional versus inflammatory DCs in innate and adaptive immune responses. The observation that monocytes may, in some conditions, differentiate into DCs was confirmed by Serbina et al. [6], in a study published back-to-back with that of Geissmann and colleagues [5]. In the course of the study by Serbina et al. [6], which aimed to identify the source of nitric oxide (NO) and tumor necrosis factor (TNF) (essential mediators produced by monocytes and DCs for the control of Listeria monocytogenes), the authors showed that infection with this bacteria induced the recruitment of a novel TNF- and iNOS-producing DC subset to the spleen.