News Alerts  May 8, 2013--------News Archive

Inside the placenta: infected red blood cells (IRBC, in green) in the maternal blood space (MBS; in red) are localized near the placental tissue (trophoblast, in blue). (A) Snap shot of a live image of the placenta and (B) schematic representation of the structures shown in A. Credits: Luciana Moraes, IGC.

Placental blood flow influences malaria during pregnancy

For the first time, mouse placental circultation was observed in live pregnancies showing how placental blood flow can influence malaria parasite behavior and infection.

Malaria in pregnancy causes a range of adverse effects, including spontaneous abortions, stillbirths, premature delivery and low infant birth weight. Many of these effects are thought to be initiated by a placental inflammatory response to parasite infected red blood cells.

In a study published in the latest issue of the journal PLoS Pathogens*, a team of researchers led by Carlos Penha-Gonçalves of the Instituto Gulbenkian de Ciência (IGC), Portugal, observed for the first time live mouse placental circulation. This observation showed that there are regions of low placental blood flow which may harbor higher accumulations of parasites, inducing an inflammatory response.

In humans, red blood cells infected with the malaria Plasmodium falciparum parasite accumulate in the placenta due to interaction with a molecule expressed on the placental tissue - in a process called sequestration.

In response to sequestration, placental cells secrete substances to recruit inflammatory cells which—in over abundance—leads to placental damage and negatively impacting fetal growth.

Until now placental circulation had not been linked to sequestration of infected red blood cells. In fact, it is impossible to investigate this hypothesis in the human placenta due to ethical constraints.

Luciana Moraes, an investigator of Carlos Penha-Gonçalves laboratory, has developed an experimental system that allows live observation of blood flow in the mouse placenta. Mating two strains of mice, one of them with cells stained with a colorful marker, Luciana was able to selectively identify the fetal origin of placental tissue.

In collaboration with Carlos Tadokoro's laboratory at the IGC, the investigators developed a microscopy technique that allowed the observation of the placenta in a living mouse. Immediately before exposure to the microscope the mouse was injected with a fluorescent substance that labels the blood. With this set-up it was possible to distinguish maternal blood and placental tissue. The results showed for the first time how the circulation occurs in the placenta, and that the blood flows with different speeds in different regions of the placenta.

Next, the investigators infected red blood cells with the malaria parasite Plasmodium berghei, stained with a different color, and observed - live - the behavior of the parasite inside the placenta. They observed that in the areas with higher blood flow, the parasite never stops moving and does not interact with the placental tissue. The accumulation of parasite just occurs in areas of low or absence of flow. In these regions, placental macrophages engulf the infected red blood cells to attempt parasite clearance. Their observations also suggest that movements of the placental tissue may control the blood flow.

Luciana Moraes says: "Our results indicate that binding of infected red blood cells to a molecule expressed in the placenta may not be the only mechanism of parasite sequestration. The dynamics of placental circulation may also play an important role, and should be considered when designing therapeutics."

Carlos Penha-Gonçalves adds: "This is the first study done that shows live how placental blood circulation impacts on the local infection by the malaria parasite. It would be interesting and worthwhile to explore if a similar process occurs in the placenta of humans, taking in consideration that microcirculation in human placenta is quite different."

This study was done in collaboration with University of Vigo, Spain, and was funded by Fundação para a Ciência e a Tecnologia, Portugal.

* de Moraes LV, Tadokoro CE, Gómez-Conde I, Olivieri DN, Penha-Gonçalves C (2013) Intravital Placenta Imaging Reveals Microcirculatory Dynamics Impact on Sequestration and Phagocytosis of Plasmodium-Infected Erythrocytes. PLoS Pathog 9(1): e1003154. doi:10.1371/journal.ppat.1003154.

For further information, please contact, Ana Mena, Tel. +351 21 440 7959

Original article: http://www.igc.gulbenkian.pt/pages/article.php/A=274___collection=pressReleases___year=2013