Blood monocytes: distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T‐cell responses

Abstract

Monocytes can have important effects on the polarization and expansion of lymphocytes and may contribute to shaping primary and memory T‐cell responses in humans and mice. However, their precise contribution in terms of cellular subsets and the molecular mechanisms involved remains to be determined. Mouse monocytes originate from a bone marrow progenitor, the macrophage and DC precursor (MDP), which also gives rise to conventional dendritic cells through a separate differentiation pathway. Mouse monocytes may be grouped in different functional subsets. The CD115+ Gr1+ ‘inflammatory’ monocyte subset can give rise not only to immunostimulatory ‘TipDCs’ in infected mice but also to immunosuppressive ‘myeloid‐derived suppressor cells’ in tumor‐bearing mice. CD115+ Gr1+ monocytes can also contribute to the renewal of several resident subsets of macrophages and DCs, such as microglia and Langerhans cells, in inflammatory conditions. The CD115+ Gr1− ‘resident’ monocyte subset patrols blood vessels in the steady state and extravasates during infection with Listeria monocytogenes or in the healing myocardium. CD115+ Gr1− monocytes are responsible for an early and transient inflammatory burst during Lm infection, which may play a role in the recruitment of other effector cells and subsequently differentiate toward ‘M2’‐like macrophages that may be involved in wound healing. More research will no doubt confirm the existence of more functional subsets, the developmental relationship between mouse subsets as well as the correspondence between mouse subsets and human subsets of monocytes. We will discuss here the potential roles of monocytes in the immune response, the existence of functional subsets and their relationship with other myeloid cells, including dendritic cells.

In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses

“…Accessory cells such as monocytes can be activated in situ by several mechanisms, including signaling through Toll-like receptors or nucleotide-binding oligomerization domain (NOD)-like receptors by pathogens or danger signals, via cytokineactivation, or by T cell-mediated CD40-ligation (29)(30)(31)(32). The specific signaling cascades induced by each of these stimuli are likely to affect the way in which monocytes and T cells interact, and, thus, the ensuing T cell response.…”

Monocyte and neutrophil recruitment during oral Salmonella infection is driven by MyD88‐derived chemokines

“…They develop in the bone marrow, are released into the circulation and enter tissues in response to infection. Murine monocytes in the blood are a heterogeneous population and have been divided into two main subsets based on whether they are present in steady state or recruited under inflammatory conditions [1]. Inflammatory Gr-1 hi CCR2 hi CX 3 CR1 low monocytes, which have also been called TipDC upon entering a tissue, are a source of molecules important in controlling bacterial infection, particularly iNOS and TNF-a [2][3][4].…”

Mycobacterium bovis Bacillus Calmette-Guérin Vaccination Mobilizes Innate Myeloid-Derived Suppressor Cells Restraining In Vivo T Cell Priming via IL-1R–Dependent Nitric Oxide Production

“…In the mouse, the different levels of CX3CR1 expression, the fractalkine receptor, and Ly-6C, a glycosylphosphatidylinositol-anchored protein, at the cell surface define two different subsets (2): CX3CR1 lo Ly-6C hi MOs migrate to inflamed tissues upon CCR2 activation of the host response against infection (3), and CX3CR1 hi Ly-6C lo CCR2 2 MOs replenish the resident tissue macrophage pool under steady-state conditions (2). Blood MOs with intermediate levels of Ly-6C may represent different differentiation phases of a continuum (4)(5)(6) or bona fide MO subsets (7). Bone marrow-derived precursors for neutrophils and MOs (8), sometimes referred to as band-cells or ring-shaped nucleus cells, also circulate under steady-state conditions (9).…”