Antigen presentation by monocytes and monocyte-derived cells

Abstract

SummaryMonocytes are circulating mononuclear phagocytes with a fundamental capacity to differentiate into macrophages. This differentiation can, in the presence of the right environmental cues, be re-directed instead to dendritic cells (DCs). Recent advances have been made in understanding the role of monocytes and their derivatives in presenting antigen to drive immune responses, and we review this topic herein. We briefly discuss the heterogeneity of monocytes in the blood and subsequently raise the possibility that one of the major monocyte phenotypes in the blood corresponds with a population of "blood DCs" previously proposed to drive T-independent antibody reactions in the spleen. Then we evaluate the role of monocytes in T-dependent immunity, considering their role in acquiring antigens for presentation prior to exiting the bloodstream and their ability to differentiate into macrophages versus antigen-presenting DCs. Finally, we review recent literature on the role of monocyte-derived cells in cross-presentation and discuss the possibility that monocyte-derived cells participate critically in processing antigen for cross-priming, even if they do not present that antigen to T cells themselves.Just recently, we participated in a group discussion with other colleagues whose research interests includes the biology of monocytes, and the discussion moved to the point of whether one can define the term "monocyte." Not all of our colleagues believed that such a definition could be clearly made in the current molecular age where cell types are readily divided up and defined by the presence and absence of an array of cell surface markers. However, we cannot approach research on the subject of monocytes without drawing a definition for these cells. Though universal agreement on this definition may not be possible, as we learned during this recent collegial exchange, the definition we adhere to is practical and a product of our training and discussion with other experts on monocytes over more than 15 years. For decades, a monocyte was identifiable morphologically and functionally as the mononuclear phagocyte in the blood [1][2][3]. Corresponding with this definition was the understanding that the cell readily differentiated into macrophages. Thus, our research on monocytes operates under the premise that monocytes are (a) mononuclear cells in the circulation with (b) the capacity for phagocytosis and (c) propensity to differentiate to macrophages at least in some settings. Some cell types, often termed circulating dendritic cells (DCs), have been identified in human blood that fit one or both of the first two parts of the definition but so far not the third [4][5][6]. So, fittingly, these latter cells are not included in the definition of monocytes. We also uphold the view that the term "monocyte" defines a cell that is in the bloodstream. Once a monocyte extravasates into tissue, a differentiation program toward macrophages or DCs begins, and the cell should no longer be referred to as a monocyte, but rather as a mo...

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