IL-10 up-regulates human monocyte phagocytosis in the presence of IL-4 and IFN-γ

Abstract

Interleukin-10 (IL-10), a cytokine produced by type 2 helper T (Th2) cells, inhibits the microbicidal effector function of interferon-gamma (IFN-gamma)-activated macrophages. However, recent observations indicate that IL-10, like IFN-gamma, increases Fc gamma RI expression and Fc gamma R-mediated cytotoxic activity on human monocytes, suggesting that this cytokine cannot be classified purely as a monocyte deactivator. The present study found that incubation for 40 h of human monocytes or monocyte-derived macrophages in the presence of IL-10 caused a significant enhancement of their capacity to ingest particles coated with immunoglobulin G (Fc gamma R-mediated ingestion) or with C3b/C3bi fragments of the complement system (CR1/CR3-mediated ingestion). The number of phagocytosing cells (% phagocytosis) and the number of ingested particles per cell (phagocytic index) were both significantly higher after 40-h incubation of monocytes with IL-10 concentrations > or = 1 U/ml. This up-regulating activity on phagocytosis was completely reversed by anti-IL-10 monoclonal antibody (mAb). As previously reported, IL-10 stimulated Fc gamma RI expression on monocytes but did not induce the expression of Fc gamma RII, Fc gamma RIII, CR1, and CR3. IFN-gamma, like IL-10, up-regulated only Fc gamma RI expression but significantly reduced both Fc gamma R- and CR-mediated ingestion. IL-10 almost completely reversed the IFN-gamma-induced inhibition of both Fc gamma R- and CR-mediated phagocytosis, without concomitant changes in membrane expression of phagocytic receptors. Exposure of monocytes to IL-4 reduced the membrane expression of all three Fc gamma Rs and also inhibited Fc gamma R-mediated ingestion. On the other hand, IL-4 up-regulated both CR3 expression and CR-mediated ingestion on cultured monocytes. IL-10 not only neutralized the down-regulatory effect of IL-4 on Fc gamma R expression but also completely reversed the IL-4-induced suppression of Fc gamma R-mediated phagocytosis. Exposure of monocytes to a combination of IL-10 and IL-4 resulted in a synergistic effect on CR-mediated ingestion, even though no additive effects were observed on CR membrane expression. Finally, culture of monocytes in medium containing anti-IL-10 mAb significantly reduced their capacity to ingest IgG- or C3b/C3bi-coated particles, suggesting a role for endogenously produced IL-10 in the modulation of phagocytosis by human monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Multi-peptide coupled-cell tolerance ameliorates ongoing relapsing EAE associated with multiple pathogenic autoreactivities

“…TGF-β suppresses the production of nitric oxide and reactive oxygen intermediates by macrophages [64][65][66] and has also been shown to inhibit the differentiation of T cells into Th1 and Th2 cells by blocking expression of T-bet and GATA-3 [67][68][69]. IL-10 has been shown to increase monocytic phagocytosis [70,71] while reducing antigen presentation and CD80/86 expression [72,73]. We are currently evaluating the requirement, or lack thereof, for natural T reg and induced Tr1 cells and/or TGF-β and IL-10 in multi-peptide coupled-cell tolerance utilizing GFP-Foxp3 knock-in mice [74].…”

“…To determine whether multiple myelin peptides could be coupled to syngeneic splenocytes and presented to naïve CD4 + T cells efficiently enough to protect against EAE induced with individual myelin peptides as well as multiple myelin peptides, SJL mice were given 50×10 6 syngeneic splenocytes coupled to four encephalitogenic myelin peptides (PLP 139-151 , PLP [178][179][180][181][182][183][184][185][186][187][188][189][190][191] , MBP 84-104 , and MOG 92-106 ) (Tolerized) or four irrelevant peptides (PLP [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] , OVA 323-339 , VP1 233-250 , and VP2 [70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] ) (Sham) seven days before priming with each peptide individually (Figure 1), or a combination of all four encephalitogenic myelin peptides ( Figure 2). Not only did the tolerization protocol completely prevent or drastically reduce clinical symptoms in every situation, but DTH resp...…”

“…To test this, female SJL mice were primed with PLP 139-151 or PLP [178][179][180][181][182][183][184][185][186][187][188][189][190][191] , which both result in relapsing-remitting disease in which the first relapse is due to intramolecular epitope spreading [15][16][17]. At the peak of acute disease, during which there is only CD4 + T cell reactivity to the initiating epitope, 50 × 10 6 syngeneic splenocytes coupled to four encephalitogenic myelin peptides (PLP 139-151 , PLP [178][179][180][181][182][183][184][185][186][187][188][189][190][191] , MBP 84-104 , and MOG 92-106 ) (Tolerized), including both the initiating and spread epitopes, or four irrelevant peptides (PLP [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] , OVA 323-339 , VP1 233-250 , and VP2 [70][71][72][73][74]…”

Candida parapsilosis produces prostaglandins from exogenous arachidonic acid and OLE2 is not required for their synthesis

“…In addition to increased phagocytosis and killing, OLE2 mutants also stimulated higher IL-10 production in macrophages compared to WT cells. IL-10 has been shown to increase the phagocytic capacity of macrophages 28 ; therefore, suppression of IL-10 secretion may also be beneficial for the pathogen during infection.…”

Interleukin-10 Has Different Effects on Proliferation ofListeria monocytogenesin Livers and Spleens of Mice

“…Furthermore, IL-10 downregulates macrophage functions such as the secretion of proinflammatory cytokines like tumor necrosis factor alpha (TNF) and interleukin-12 (IL-12) (10) and the production of reactive oxygen intermediates and reactive nitrogen intermediates (3). However, IL-10 stimulates B cells (14), enhances T-cell proliferation (7,23) and differentiation (6), increases Fc␥R expression on monocytes (35), and enhances phagocytosis by monocytes (5).…”