Cellular immune response to Plasmodium falciparum after pregnancy is related to previous placental infection and parity

BACKGROUND: Malaria in pregnancy is characterised by the sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces. Placental parasites express a specific phenotype, which allows them to cytoadhere to chondroitin sulfate A expressed by syncytiotrophoblasts. Malaria infection during pregnancy allows the acquisition of antibodies against placental parasites, these antibodies are thought to be involved in protection during subsequent pregnancies. METHODS: To investigate the development of a cellular response to placental parasites during pregnancy, peripheral blood mononuclear cells were collected from women at the time of their confinement. The study was performed in Cameroon where malaria transmission is perennial. In vitro cell proliferation and cytokine production were measured in response to non-malarial activators (concanavalin A and PPD), a recombinant protein from P. falciparum MSP-1, and erythrocytes infected by two P. falciparum lines, RP5 and W2. Like placental parasites, the RP5 line, but not W2, adheres to chondroitin sulfate A and to syncytiotrophoblasts. RESULTS: The proliferative response to all antigens was lower for cells obtained at delivery than 3 months later. Most interestingly, the cellular response to the RP5 line of P. falciparum was closely related to parity. The prevalence rate and the levels of response gradually increased with the number of previous pregnancies. No such relationship was observed with W2 line, or MSP-1 antigen. CONCLUSIONS: This suggests the occurrence of an immune response more specific for the RP5 line in women having had multiple pregnancies, and who are likely to develop immunity to pregnancy-associated parasites. Both humoral and cellular mechanisms may account for the lower susceptibility of multigravidae to malaria

Higher placental anti-inflammatory IL-10 cytokine expression in HIV-1 infected women receiving longer zidovudine prophylaxis associated with nevirapine

Placental cytokine balance may be critical for the control of mother-to-child transmission (MTCT) of HIV. We assessed whether the type and duration of antiretrovirals used for prevention of HIV-1-MTCT modified the inflammatory cytokine profile. We investigated the levels of cytokine expression in the placentas of 61 HIV-1-infected women who received zidovudine (ZDV) plus single dose nevirapine (SD-NVP) or ZDV only for prevention of MTCT. Placentas of 38 HIV-1-uninfected women were included as controls. All placentas were obtained after vaginal delivery. Levels of mRNA and cytokine expression were quantified using real-time PCR and ELISA, respectively, in placental explants and 24-hour culture supernatants and analyzed in relation to the women's characteristics and the type and duration of antiretroviral prophylaxis. HIV-1-infected and uninfected women did not show any differences in the expression of placental cytokine secretion except for a trend toward lower TNF-10 mRNA levels in HIV-1-infected women. Within the HIV-1-infected group, women who were exposed to a long duration of ZDV (>72 days) or received SD-NVP less than 5h prior to delivery, more frequently expressed detectable levels of IL-10 in their placentas (32% versus 7% (p = 0.01) and 32% versus 5% (p = 0.02), respectively). No infant was found to be HIV-1-infected. Our results showed a normalization of the placental cytokine balance in HIV-1-infected women receiving antiretroviral prophylaxis. Furthermore, the type and duration of antiretroviral prophylaxis have an impact on the placental anti-inflammatory IL-10 expression level, which may contribute to controlling HIV replication at the placental level, thus reducing MTCT of HIV-1.Fil: Pornprasert, Sakorn. Chiang Mai University; TailandiaFil: Mary, Jean-Yves. Université Paris Diderot - Paris 7; FranciaFil: Faye, Albert. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Leechanachai, Pannee. Chiang Mai University; TailandiaFil: Limtrakul, Aram. Health Promotion Center Region; TailandiaFil: Rugpao, Sungwal. Chiang Mai University; TailandiaFil: Sirivatanapa, Pannee. Chiang Mai University; TailandiaFil: Gomuthbutra, Vorapin. Nakornping Hospital; TailandiaFil: Matanasaravoot, Wanmanee. Lamphun Hospital; TailandiaFil: Le Coer, Sophie. Institut National d’Etudes Démographiques; FranciaFil: Lallemant, Marc. Centre National de la Recherche Scientifique. Institut de Recherche pour le Développement; FranciaFil: Barré-Sinoussi, Françoise. Instituto Pasteur; FranciaFil: Menu, Elisabeth. Instituto Pasteur; FranciaFil: Ngo Giang Huong, Nicole. Centre National de la Recherche Scientifique. Institut de Recherche pour le Développement; FranciaFil: Ayouba, Ahidjo. Instituto Pasteur; FranciaFil: Chailert, Sanupong. Chiang Mai University; Tailandia. Instituto Pasteur; FranciaFil: Chaouat, Gérard. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Derrien, Muriel. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Dolcini, Guillermina Laura. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Sanidad Animal y Medicina Preventiva. Laboratorio de Virología; Argentina. Instituto Pasteur; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Eteki, Nicole. Hôpital Central de Yaoundé. Maternité Principale; CamerúnFil: Kfutwah, Anfumbom Jude. Instituto Pasteur; FranciaFil: Kouo, Odette. Instituto Pasteur; FranciaFil: Lemen, Brigitte. Instituto Pasteur; FranciaFil: Abal, Facundo Juan Pablo. Instituto Pasteur; FranciaFil: Nerrienet, Eric. Instituto Pasteur; FranciaFil: Njinku, Bernadette. Instituto Pasteur; FranciaFil: Scarlatti, Gabriella. Suan Dok Hospital; TailandiaFil: Tejiokem, Mathurin. Centre Pasteur du Cameroun; CamerúnFil: Téné, Gilbert. No especifíca

TWEAK Appears as a Modulator of Endometrial IL-18 Related Cytotoxic Activity of Uterine Natural Killers

BACKGROUND: TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implantation window, using an ex-vivo endometrial microhistoculture model. Indeed, previous results suggested that basic TWEAK expression influences the IL-18 related uNK recruitment and local cytotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Endometrial biopsies were performed 7 to 9 days after the ovulation surge of women in monitored natural cycles. Biopsies were cut in micro-pieces and cultured on collagen sponge with appropriate medium. Morphology, functionality and cell death were analysed at different time of the culture. We used this ex vivo model to study mRNA expressions of NKp46 (a uNK cytotoxic receptor) and TGF-beta1 (protein which regulates uNK cytokine production) after adjunction of excess of recombinant IL-18 and either recombinant TWEAK or its antibody. NKp46 protein expression was also detailed by immunohistochemistry in selected patients with high basic mRNA level of IL-18 and either low or high mRNA level of TWEAK. The NKp46 immunostaining was stronger in patients with an IL-18 over-expression and a low TWEAK expression, when compared with patients with both IL-18 and TWEAK high expressions. We did not observe any difference for TWEAK expression when recombinant protein IL-18 or its antibody was added, or conversely, for IL-18 expression when TWEAK or its antibody was added in the culture medium. In a pro-inflammatory environment (obtained by an excess of IL-18), inhibition of TWEAK was able to increase significantly NKp46 and TGF-beta1 mRNA expressions. CONCLUSIONS/SIGNIFICANCE: TWEAK doesn't act on IL-18 expression but seems to control IL-18 related cytotoxicity on uNK cells when IL-18 is over-expressed. Thus, TWEAK appears as a crucial physiological modulator to prevent endometrial uNK cytotoxicity in human

More than a decade of debates in the preeclampsia (island) workshops: a (personally biased) evolutionary perspective.

International audienceIn this short remembrance paper, I survey (what I believe are) key events in the evolution of the concepts of preeclampsia from the first workshop in 1998 to the 2012 one, and from Tahiti to Reunion island, via Mauritius and Tioman Island

Les follicules antraux (maitrise de leur croissance et production d'hormone anti-müllérienne chez la femme)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Environnement cytokinique placentaire (rôle et modulation dans le cadre de la prévention de la transmission mère-enfant du virus de l' immunodéficience humaine de type 1 par des antirétroviraux)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

CYTOKINES ET CHIMIOKINES PLACENTAIRES ET TRANSMISSION MATERNO-FOETALE DU VIRUS DE L'IMMUNODEFICIENCE HUMAINE DE TYPE 1 (DOCTORAT (IMMUNOLOGIE))

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Expression membranaire/intracellulaire des récepteurs de chimiokines CXCR4/CCR5 par les cellules de cytotrophoblaste villeux de placenta humain précoce / à terme et de choriocarcinome : effet des cytokines proinflammatoires

RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Implication de mécanismes immunologiques dans les échecs d'implantation embyonnaire et les avortements en modèles humain et murin

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF