Placental Malaria-Associated Suppression of Parasite-Specific Immune Response in Neonates Has No Major Impact on Systemic CD4 T Cell Homeostasis
Infection and Immunity, July 2011,p. 2801-2809, Vol. 79, No. 7: 019-9567/11/$12.00+0 doi:10.1128/IAI.00203-11
Valérie Soulard,1,2,* Martin Amadoudji Zin,3 Catherine Fitting,4 Samad Ibitokou,3 Mayke Oesterholt,5 Adrian J. F. Luty,5 René-Xavier Perrin,6Achille Massougbodji,3 Philippe Deloron,1,2,* Antonio Bandeira,7, and Nadine Fievet1,2
1Institut de Recherche pour le Développement UMR216 Santé de la Mère et l'Enfant en Milieu Tropical 2Université Paris Descartes, Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006 Paris, France 3Parasitology and Mycology Education and Research Unit, Science and Health Faculty, BP 188 Cotonou, Benin 4Cytokines and Inflammation, Department of Infection and Epidemiology, Institut Pasteur, Paris, France 5Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands 6Science and Health Faculty, BP 188 Cotonou, Benin 7Lymphocyte Development Unit, Department of Immunology, Institut Pasteur, Paris, France
In areas where Plasmodium falciparum is endemic, pregnancy is associated with accumulation of infected red blood cells (RBCs) in the placenta, a condition referred to as placental malaria (PM). Infants born to PM-positive mothers are at an increased risk ofmalaria, which is putatively related to the transplacental passage of parasite-derived antigens, with consequent tolerization of the fetal immune system. Here we addressed the impact of PM on the regulation of neonatal T cell responses. We found that the frequency of regulatory CD25+ CD127–/low Foxp3+ CD4+ T cells was significantly decreased in neonates born to mothers with high levels of P. falciparum-induced placental inflammation, consisting mainly of primigravid mothers. However, at the individual level, the ratio between regulatory and effector (CD25+CD127+ Foxp3–) CD4+ T cells was unaffected by PM. In addition, parasite-induced CD4+ T cell activation and production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-10 were strongly reduced in neonates born to PM-positive mothers. Thus, our results show that active PM at delivery is associated with a marked suppression of P. falciparum-specific cellular neonatal immune responses, affecting secretion of both pro- and anti-inflammatory cytokines. Additionally, our results suggest that, as in adults, effector and regulatory CD4+ T cell populations are tightly coregulated in all neonates, irrespective of the maternal infection status.
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* Corresponding author. Mailing address for Philippe Deloron: IRD UMR 216 Santé de la Mère et l'Enfant en Milieu Tropical, Université Paris Descartes, 4 Av. de l'Observatoire, 75006 Paris, France. Phone: 33 1 53 73 96 22. Fax: 33 1 53 73 96 17. E-mail: philippe.deloron@ird.fr. Present address for Valérie Soulard: Inserm U986, Hôpital Saint- Vincent de Paul, 82 Av. Denfert-Rochereau, 75014 Paris, France. Phone: 33 1 43 21 72 98. Fax: 33 1 40 48 83 52. E-mail:valerie_soulard@yahoo.fr.
Infection and Immunity, July 2011,p. 2801-2809, Vol. 79, No. 7: 019-9567/11/$12.00+0 doi:10.1128/IAI.00203-11
Valérie Soulard,1,2,* Martin Amadoudji Zin,3 Catherine Fitting,4 Samad Ibitokou,3 Mayke Oesterholt,5 Adrian J. F. Luty,5 René-Xavier Perrin,6Achille Massougbodji,3 Philippe Deloron,1,2,* Antonio Bandeira,7, and Nadine Fievet1,2
1Institut de Recherche pour le Développement UMR216 Santé de la Mère et l'Enfant en Milieu Tropical 2Université Paris Descartes, Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006 Paris, France 3Parasitology and Mycology Education and Research Unit, Science and Health Faculty, BP 188 Cotonou, Benin 4Cytokines and Inflammation, Department of Infection and Epidemiology, Institut Pasteur, Paris, France 5Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands 6Science and Health Faculty, BP 188 Cotonou, Benin 7Lymphocyte Development Unit, Department of Immunology, Institut Pasteur, Paris, France
In areas where Plasmodium falciparum is endemic, pregnancy is associated with accumulation of infected red blood cells (RBCs) in the placenta, a condition referred to as placental malaria (PM). Infants born to PM-positive mothers are at an increased risk ofmalaria, which is putatively related to the transplacental passage of parasite-derived antigens, with consequent tolerization of the fetal immune system. Here we addressed the impact of PM on the regulation of neonatal T cell responses. We found that the frequency of regulatory CD25+ CD127–/low Foxp3+ CD4+ T cells was significantly decreased in neonates born to mothers with high levels of P. falciparum-induced placental inflammation, consisting mainly of primigravid mothers. However, at the individual level, the ratio between regulatory and effector (CD25+CD127+ Foxp3–) CD4+ T cells was unaffected by PM. In addition, parasite-induced CD4+ T cell activation and production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-10 were strongly reduced in neonates born to PM-positive mothers. Thus, our results show that active PM at delivery is associated with a marked suppression of P. falciparum-specific cellular neonatal immune responses, affecting secretion of both pro- and anti-inflammatory cytokines. Additionally, our results suggest that, as in adults, effector and regulatory CD4+ T cell populations are tightly coregulated in all neonates, irrespective of the maternal infection status.
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* Corresponding author. Mailing address for Philippe Deloron: IRD UMR 216 Santé de la Mère et l'Enfant en Milieu Tropical, Université Paris Descartes, 4 Av. de l'Observatoire, 75006 Paris, France. Phone: 33 1 53 73 96 22. Fax: 33 1 53 73 96 17. E-mail: philippe.deloron@ird.fr. Present address for Valérie Soulard: Inserm U986, Hôpital Saint- Vincent de Paul, 82 Av. Denfert-Rochereau, 75014 Paris, France. Phone: 33 1 43 21 72 98. Fax: 33 1 40 48 83 52. E-mail:valerie_soulard@yahoo.fr.
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