Induction of pro-inflammatory response of the placental trophoblast by Plasmodium falciparum infected erythrocytes and TNF

Vásquez, Ana María; Segura, Cesar; Blair, Silvia

doi:10.1186/1475-2875-12-421

Cited by 21 publications

(18 citation statements)

References 32 publications

(51 reference statements)

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“…This observation suggests that increased P. berghei-VAR IE adherence is probably related to the presence of a var2CSA DBL1-6 domain, which might exhibit stronger binding properties than P. berghei proteins. It has been shown that less adherent strains of P. falciparum induced lower release of proinflammatory factors by BeWO cells (a trophoblast model) in vitro, suggesting that the magnitude of inflammation is associated with the affinity of IE adherence (27). Taken together, these data could explain why P. berghei-VAR infection results in worse pregnancy outcomes.…”

Section: Discussionmentioning

confidence: 53%

“…Published data support the notion that trophoblasts have an active role in the inflammatory process by reacting to IE adherence. In vitro studies have shown that after interaction with IEs, trophoblasts secrete interleukin 6 (IL-6) (27) and chemokines (27,31), which in turn recruit immune cells to the site of IE stimulation (31). This inflammatory environment in the placenta can affect its anatomic structure and normal function.…”

Section: Discussionmentioning

confidence: 99%

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Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated with Malaria in Pregnancy

et al. 2016

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g Plasmodium falciparum infection during pregnancy leads to abortions, stillbirth, low birth weight, and maternal mortality. Infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) via var2CSA protein exposed on the P. falciparum IE membrane. Plasmodium berghei IE infection in pregnant BALB/c mice is a model for severe placental malaria (PM). Here, we describe a transgenic P. berghei parasite expressing the full-length var2CSA extracellular region (domains DBL1X to DBL6) fused to a P. berghei exported protein (EMAP1) and characterize a var2CSA-based mouse model of PM. BALB/c mice were infected at midgestation with different doses of P. berghei-var2CSA (P. berghei-VAR) or P. berghei wild-type IEs. Infection with 10 4 P. berghei-VAR IEs induced a higher incidence of stillbirth and lower fetal weight than P. berghei. At doses of 10 5 and 10 6 IEs, P. berghei-VAR-infected mice showed increased maternal mortality during pregnancy and fetal loss, respectively. Parasite loads in infected placentas were similar between parasite lines despite differences in maternal outcomes. Fetal weight loss normalized for parasitemia was higher in P. berghei-VAR-infected mice than in P. berghei-infected mice. In vitro assays showed that higher numbers of P. berghei-VAR IEs than P. berghei IEs adhered to placental tissue. Immunization of mice with P. berghei-VAR elicited IgG antibodies reactive to DBL1-6 recombinant protein, indicating that the topology of immunogenic epitopes is maintained between DBL1-6 -EMAP1 on P. berghei-VAR and recombinant DBL1-6 (recDBL1-6). Our data suggested that impairments in pregnancy caused by P. berghei-VAR infection were attributable to var2CSA expression. This model provides a tool for preclinical evaluation of protection against PM induced by approaches that target var2CSA. Malaria is a major health concern in countries where it is endemic. Recent reports show an incidence of 198 million cases in 2013 (82% in Africa) and 584,000 estimated deaths, 74% of which were children under 5 years of age (1). In areas of endemicity, pregnant women are under a greater risk of malaria than nonpregnant (NP) women due to immunological and hormonal changes and higher attractiveness to mosquitoes (2). Placental infection or clinical malaria during pregnancy has been shown to have a negative impact on infant health, increasing the risk of clinical malaria and mortality in infants (3).In areas of unstable malaria transmission, pregnant women can develop severe malaria due to low immunity to the parasite, which has been associated with increased mortality during pregnancy (4, 5), miscarriages, preterm deliveries, low birth weight, stillbirth, and death of neonates (6). These features can be recapitulated in a mouse model of severe placental malaria (PM) (7), which consists of infection of BALB/c mice syngeneically pregnant with parasites of the ANKA strain of the rodent malaria parasite Plasmodium berghei.Apart from physiological changes associated with gestation, increased suscep...

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated with Malaria in Pregnancy

et al. 2016

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“…An increase of IL10, that has an anti-inflammatory role and a negative feedback on TNF, has specificity and sensibility of placental inflammation in PAM [51]. The immune response to CSA-binding iE involves TNF and its receptors TNF-R1 and R2.…”

Section: Introductionmentioning

confidence: 99%

“…The immune response to CSA-binding iE involves TNF and its receptors TNF-R1 and R2. They stimulate the phagocytic activity of leukocytes by increasing ICAM-1 expression and the pro-inflammatory response by favouring the liberation of IL6 and IL8 [51]. Other biomarkers have been described as increased in the peripheral blood during PAM: IL1, IL10, TNF, TNF-R1, TNF-R2 and IFN-γ [52, 53].…”

Section: Introductionmentioning

confidence: 99%

Usefulness of a biomarker to identify placental dysfunction in the context of malaria

Gueneuc

Deloron

Bertin

2017

Malar J

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In most tropical areas, pregnant women are at increased risk of malaria, as a consequence of the massive sequestration of parasitized red blood cells in the placenta. The placenta plays a key role in embryonic and fetal development as well as in maternal-fetal exchanges, and pregnancy-associated malaria may alter selected placenta functions that lead to stillbirth and low birth weight. Although there are several tools (blood smear examination, RDT, PCR) to diagnose malaria infection during pregnancy, there is currently no test to assess placenta dysfunction in the framework of pregnancy-associated malaria. Pregnancy-associated malaria shares many features with preeclampsia, an extensively studied disease. Various biomarkers associated with placental dysfunction have been identified as associated with preeclampsia. Several of these are inflammatory markers that lack of specificity. A few seem more specific of placenta dysfunction, including s-endoglin and sFlt1, increased in the peripheral blood during preeclampsia. The predictive value of these biomarkers should be studied in the context of pregnancy-associated malaria to evaluate their usefulness in identifying placental dysfunction during malaria. These biomarkers should be considered to improve the diagnosis of placental dysfunction during malaria and pregnant women monitoring.

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“…Uno de los principales glicanos presentes en la placenta, identificado como el receptor por excelencia de eritrocitos parasitados con Plasmodium spp en este tejido es el CSA. En un estudio realizado por Vásquez y cols (32), mencionan que el CSA podría estar actuando indirectamente como inductor de inflamación de la placenta en MP por P. falciparum y otros estudios recientes ponen de manifiesto la participación de esta molécula como regulador de la inflamación en diversos modelos biológicos tales como la enfermedad de Bowel y reparación de diversos tejidos lesionados (33,34).…”

Section: Glicosaminoglicanos Citoadherencia E Inflamaciónunclassified

Glicosaminoglicanos como posibles reguladores de inflamación durante la malaria placentaria

2014

Rev. chil. obstet. ginecol.

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a Microbióloga, MSc Biología. RESUMENLos mecanismos fisiopatológicos de la malaria placentaria son hasta el momento poco comprendidos, y el daño placentario derivado de la infección por Plasmodium spp se ha relacionado con eventos adversos del embarazo que afectan directamente el desarrollo del feto. Las concentraciones placentarias de algunas citocinas como la IL-10, TNF-α y TGF-β y glicosaminoglicanos como el CSA, HA y HS podrían estar participando de forma reguladora en los eventos inflamatorios placentarios durante la infección por Plasmodium spp.PALABRAS CLAVE: Malaria placentaria, inflamación placentaria, citosinas, placenta, glicosaminoglicanos SUMMARYThe pathophysiological mechanisms of placental malaria are until now poorly understood and the placental damage resulting from infection by Plasmodium spp has been linked to adverse pregnancy events that directly affect fetal development. Placental concentrations of some cytokines such as IL-10, TNF-α and TGF-β and glycosaminoglycans such as CSA, HA and HS could be involved in a regulatory role in placental inflammation during infection by Plasmodium spp. KEY WORDS: Placental malaria, placental inflamation, cytokines, placenta, glycosaminoglycans INTRODUCCIÓNEn áreas de transmisión para la malaria, después de los niños menores de cinco años, las gestantes son la población más susceptible para contraer la infección, debido tanto a los cambios hormonales como a las variaciones en la respuesta inmune (1), que aún siendo condiciones fisiológicas propias del embarazo, predisponen a la gestante a un mayor riesgo frente a las infecciones. La susceptibilidad es aún mayor en mujeres nunca antes expuestas a la malaria, debido principalmente a la falta de patrones inmunitarios frente a la presencia del parásito, que se construyen tras sucesivos episodios de malaria.Para evadir la respuesta inmune, Plasmodium spp hace que las formas maduras del parásito se secuestren en los lechos vasculares de órganos

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Induction of pro-inflammatory response of the placental trophoblast by Plasmodium falciparum infected erythrocytes and TNF

Cited by 21 publications

References 32 publications

Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated with Malaria in Pregnancy

Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated with Malaria in Pregnancy

Usefulness of a biomarker to identify placental dysfunction in the context of malaria

Glicosaminoglicanos como posibles reguladores de inflamación durante la malaria placentaria

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