Cargando…

IgE Mediates Killing of Intracellular Toxoplasma gondii by Human Macrophages through CD23-Dependent, Interleukin-10 Sensitive Pathway

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 surfa...

Descripción completa

Detalles Bibliográficos
Autores principales: Vouldoukis, Ioannis, Mazier, Dominique, Moynet, Daniel, Thiolat, Denis, Malvy, Denis, Mossalayi, M. Djavad
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081288/
https://www.ncbi.nlm.nih.gov/pubmed/21526166
http://dx.doi.org/10.1371/journal.pone.0018289
_version_ 1782202193121640448
author Vouldoukis, Ioannis
Mazier, Dominique
Moynet, Daniel
Thiolat, Denis
Malvy, Denis
Mossalayi, M. Djavad
author_facet Vouldoukis, Ioannis
Mazier, Dominique
Moynet, Daniel
Thiolat, Denis
Malvy, Denis
Mossalayi, M. Djavad
author_sort Vouldoukis, Ioannis
collection PubMed
description 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION: 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.
format Text
id pubmed-3081288
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-30812882011-04-27 IgE Mediates Killing of Intracellular Toxoplasma gondii by Human Macrophages through CD23-Dependent, Interleukin-10 Sensitive Pathway Vouldoukis, Ioannis Mazier, Dominique Moynet, Daniel Thiolat, Denis Malvy, Denis Mossalayi, M. Djavad PLoS One Research Article 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION: 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. Public Library of Science 2011-04-22 /pmc/articles/PMC3081288/ /pubmed/21526166 http://dx.doi.org/10.1371/journal.pone.0018289 Text en Vouldoukis et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Vouldoukis, Ioannis
Mazier, Dominique
Moynet, Daniel
Thiolat, Denis
Malvy, Denis
Mossalayi, M. Djavad
IgE Mediates Killing of Intracellular Toxoplasma gondii by Human Macrophages through CD23-Dependent, Interleukin-10 Sensitive Pathway
title IgE Mediates Killing of Intracellular Toxoplasma gondii by Human Macrophages through CD23-Dependent, Interleukin-10 Sensitive Pathway
title_full IgE Mediates Killing of Intracellular Toxoplasma gondii by Human Macrophages through CD23-Dependent, Interleukin-10 Sensitive Pathway
title_fullStr IgE Mediates Killing of Intracellular Toxoplasma gondii by Human Macrophages through CD23-Dependent, Interleukin-10 Sensitive Pathway
title_full_unstemmed IgE Mediates Killing of Intracellular Toxoplasma gondii by Human Macrophages through CD23-Dependent, Interleukin-10 Sensitive Pathway
title_short IgE Mediates Killing of Intracellular Toxoplasma gondii by Human Macrophages through CD23-Dependent, Interleukin-10 Sensitive Pathway
title_sort ige mediates killing of intracellular toxoplasma gondii by human macrophages through cd23-dependent, interleukin-10 sensitive pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081288/
https://www.ncbi.nlm.nih.gov/pubmed/21526166
http://dx.doi.org/10.1371/journal.pone.0018289
work_keys_str_mv AT vouldoukisioannis igemediateskillingofintracellulartoxoplasmagondiibyhumanmacrophagesthroughcd23dependentinterleukin10sensitivepathway
AT mazierdominique igemediateskillingofintracellulartoxoplasmagondiibyhumanmacrophagesthroughcd23dependentinterleukin10sensitivepathway
AT moynetdaniel igemediateskillingofintracellulartoxoplasmagondiibyhumanmacrophagesthroughcd23dependentinterleukin10sensitivepathway
AT thiolatdenis igemediateskillingofintracellulartoxoplasmagondiibyhumanmacrophagesthroughcd23dependentinterleukin10sensitivepathway
AT malvydenis igemediateskillingofintracellulartoxoplasmagondiibyhumanmacrophagesthroughcd23dependentinterleukin10sensitivepathway
AT mossalayimdjavad igemediateskillingofintracellulartoxoplasmagondiibyhumanmacrophagesthroughcd23dependentinterleukin10sensitivepathway