title: Placental malaria-associated suppression of parasite-specific immune response in neonates has no major impact on systemic CD4 T cell homeostasis.
abstract: 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 of malaria, 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.
authors.affiliation: Faculté de Pharmacie, Institut de Recherche pour le Développement UMR216 Santé de la Mère et l'Enfant en Milieu Tropical, Université Paris Descartes, 4 Avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Soulard
authors.forename: Martin
authors.initials: M
authors.lastname: Amadoudji Zin
authors.forename: Catherine
authors.initials: C
authors.lastname: Fitting
authors.forename: Samad
authors.initials: S
authors.lastname: Ibitokou
authors.forename: Mayke
authors.initials: M
authors.lastname: Oesterholt
authors.forename: Adrian J F
authors.initials: AJ
authors.lastname: Luty
authors.forename: René-Xavier
authors.initials: RX
authors.lastname: Perrin
authors.forename: Achille
authors.initials: A
authors.lastname: Massougbodji
authors.forename: Philippe
authors.initials: P
authors.lastname: Deloron
authors.forename: Antonio
authors.initials: A
authors.lastname: Bandeira
authors.forename: Nadine
authors.initials: N
authors.lastname: Fievet
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006706:Homeostasis; D006801:Humans; D007111:Immunity, Cellular; D007231:Infant, Newborn; D007249:Inflammation; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology*; D010920:Placenta / Q000276:immunology* / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D053699:Interleukin-7 Receptor alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10