title: IgE mediates killing of intracellular Toxoplasma gondii by human macrophages through CD23-dependent, interleukin-10 sensitive pathway.
abstract: BACKGROUND
  In 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.
  
  
  RESULTS
  Human 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.
  
  
  CONCLUSIONS
  Thus, 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.
authors.affiliation: Inserm U511, Université Pierre et Marie Curie, Paris, France.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vouldoukis
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.forename: Daniel
authors.initials: D
authors.lastname: Moynet
authors.forename: Denis
authors.initials: D
authors.lastname: Thiolat
authors.forename: Denis
authors.initials: D
authors.lastname: Malvy
authors.forename: M Djavad
authors.initials: MD
authors.lastname: Mossalayi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000469:parasitology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000201:enzymology / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010271:Parasites / Q000166:cytology / Q000187:drug effects; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014122:Toxoplasma / Q000166:cytology* / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D009573:Nitrites; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D007073:Immunoglobulin E; D052247:Nitric Oxide Synthase Type II