IL-10 Acts As a Developmental Switch Guiding Monocyte Differentiation to Macrophages during a Murine Peritoneal Infection

Abstract

The peritoneal wash of BALB/c or C57BL/6 mice contains two populations of macrophages that differ in their level of expression of MHC class II (MHC II). Although both populations efficiently phagocytose bacteria in vivo, only the MHC IIlo population is effective at phagocytosing apoptotic cells in vivo and only the MHC IIhi population is effective at presenting Ag to T cells in vitro. Soon after induction of a peritoneal infection both of these macrophage populations are lost from the peritoneal wash fraction. Blood monocytes then enter the inflamed peritoneum and develop into new peritoneal macrophages. Whether these monocytes develop into MHC IIlo or into MHC IIhi macrophages is crucially dependent on the cytokine IL-10, which is transiently elevated in the peritoneal wash during the early phase of infection. Monocytes from CD45.1 animals transferred early in infection when the IL-10 concentration is high into congenic CD45.2 recipients develop into the MHC IIlo macrophage population. Monocytes transferred later, when the IL-10 concentration has fallen, develop into the MHC IIhi population. In infected IL-10–deficient animals monocytes fail to develop into the MHC IIlo population but can be induced to do so by exogenous application of IL-10. Finally, high numbers of wild-type monocytes injected into IL-10R1–deficient animals develop into MHC IIlo macrophages and were able by a bystander effect to induce the differentiation of the endogenous monocytes to the same fate.

Receptor-Mediated Mechanism Controlling Tissue Levels of Bioactive Lipid Oxidation Products

“…In contrast, scavenger receptors and pattern recognition receptors, such as CD36 and TLR2, respectively, are highly expressed on F4/80 hi macrophages (Online Figure IVB), which are known to be involved in phagocytosis of apoptotic cells in vivo. 28 The concentration-dependent manner of CEP-BSA binding with a clear saturation together with differential interaction with distinct cell populations suggests the involvement of specific cell surface receptors. To rule out the possibility that the binding might be mediated by BSA but not by the CEP moiety, FITC-conjugated BSA (FITC-BSA) was used as a control.…”

“…26, 27 Peritoneal macrophages are often divided into two populations, F4/80 hi and F4/80 lo macrophages. 28, 29 F4/80 lo macrophages promote immune response through antigen presentation, whereas F4/80 hi macrophages are specialized for scavenging mainly through phagocytosis. 28 …”

“…28, 29 F4/80 lo macrophages promote immune response through antigen presentation, whereas F4/80 hi macrophages are specialized for scavenging mainly through phagocytosis. 28 …”

Alcohol-Induced miR-27a Regulates Differentiation and M2 Macrophage Polarization of Normal Human Monocytes

“…IL-10 acts as a developmental switch guiding monocyte differentiation to macrophages during murine peritoneal infection (49). IL-10 prevents the differentiation of monocytes to DCs but promotes their maturation into macrophages and polarizes to alternatively activated macrophages (50, 51).…”

Interleukin 10 Receptor Signaling

“…IL10R signaling has also been shown to orchestrate the development of monocytes into different subsets of peritoneal Mϕs (Nguyen, Tran, Muller, & Jack, 2012). During early phases of peritonitis, IL10 expression is increased, and monocytes that migrate into the peritoneum develop into MHCII low Mϕs, while in the later stages when IL10 levels are decreased, monocytes differentiate into MHCII high Mϕ.…”