Abstract
BackgroundIn addition to helminthic infections, elevated serum IgE levels were observed in many protozoal infections, while their contribution during immune response to these pathogens remained unclear. As IgE/antigen immune complexes (IgE-IC) bind to human cells through FcεRI or FcεRII/CD23 surface molecules, the present study aimed to identify which functional receptor may be involved in IgE-IC interaction with human macrophages, the major effector cell during parasite infection.Methodology/Principal FindingsHuman monocyte-derived macrophages were infected with Toxoplasma gondii before being incubated with IgE-IC. IgE receptors were then identified using appropriate blocking antibodies. The activation of cells and parasiticidal activity were evaluated by mediator quantification and direct counting of infected macrophages. RNAs were extracted and cell supernatants were also collected for their content in tumor necrosis factor (TNF)-α, interleukin-10 (IL-10) and nitrites. Sera from symptomatic infected patients were also tested for their content of IgE, IL-10 and nitrites, and compared to values found in healthy donors. Results showed that IgE-IC induced intracellular elimination of parasites by human macrophages. IgE-mediated effect was FcεRI-independent, but required cross-linking of surface FcεRII/CD23, cell activation and the generation of nitric oxide (NO). Although TNF-α was shown to be produced during cell activation, this cytokine had minor contribution in this phenomenon while endogenous and exogenous IL-10 down-regulated parasite killing. Inverse relationship was found between IL-10 and NO expression by infected human macrophages at both mRNA and mediator levels. The relationship between these in vitro data and in vivo levels of various factors in T. gondii infected patients supports the involvement of CD23 antigen and IL-10 expression in disease control.ConclusionThus, IgE may be considered as immune mediator during antiprotozoal activity of human macrophages through its ability to trigger CD23 signaling. Increased cell activation by IgE-IC may also account for chronic inflammatory diseases observed in some patients.
Highlights
Beside its critical role in allergy, IgE is generally believed to play a physiological role in immunity towards helminthic parasites [1]
IgE may be considered as immune mediator during antiprotozoal activity of human macrophages through its ability to trigger CD23 signaling
We recently showed that blocking CD23 by peptidic counter-structure abrogated IgE/antigen binding to human macrophages while the blocking of FceRI had no effect on these cells [17]
Summary
Beside its critical role in allergy, IgE is generally believed to play a physiological role in immunity towards helminthic parasites [1]. CD23 plays a critical role during immune response including IgE synthesis, B- and T-cell differentiation, and the secretion of inflammatory mediators by various human cells [7]. Cross-linking of surface CD23 promotes the generation of IL-1, IL-6, TNF-a, H2O2 and iNOS-mediated NO through NFkB- and AP-1dependent mechanisms [8,13,14] As both IFN-c and IL-4 promote surface CD23b expression in human macrophages, we and others demonstrated CD23 implication during both Th1 and Th2 immune responses [7,8,13]. As IgE/antigen immune complexes (IgE-IC) bind to human cells through FceRI or FceRII/CD23 surface molecules, the present study aimed to identify which functional receptor may be involved in IgE-IC interaction with human macrophages, the major effector cell during parasite infection
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