Brain microvessels endothelial cells (BMECs) compose the first layer of the blood brain barrier (BBB). BMECs are seen in cerebral malaria (CM) pathogenesis only as targets of pro-inflammatory mediators and circulatory/coagulation imbalances.

We proposed that BMECs also take part in CM development as sensors and initiators of effector immune reactions elicited by Plasmodium components or infected erythrocytes (IE).

In particular, we plan to investigate the crosstalk of BMECs with other cell types at the BBB during malaria infection using co-culture systems (3D, microfluidics platforms) and tissue-restricted gene deletion models.

This research will delineate a map of interactions within BBB components detailing sensors and pathways of innate signaling and patterns of activation in cells of the BBB induced by exposure to IE that likely will be relevant to other infectious encephalopathies.

Liver resident macrophages (Kupffer cells) play critical roles in the response to liver injury.

Researchers are investigating liver recovery after hepatotoxic damage, which induces profound depletion of Kupffer cells followed by macrophage repopulation.

The findings indicate that hepatotoxic liver damage imposes alterations in the ontogenic composition of the post-recovery liver macrophage populations with Kupffer-like phenotype (e.g. high representation of hematopoietic-derived macrophages).

Researchers want to uncover the role of macrophages in resolution of liver damage by asking whether in the aftermath of an initial hepatotoxic injury macrophage phenotypic adaptation improves hepatic tissue resilience to subsequent challenges.

They expect this research to highlight how phenotypic plasticity of non-parenchymal cell-types (particularly macrophages) protects tissues against prolonged or multiple insults.

Fetal-derived syncytialized trophoblasts are posed at placental barrier in direct contact with maternal blood.

Using experimental models we investigated the pathogenesis of placental infection by the malaria parasite and found two unanticipated turns:

• A conflict between the innate maternal responses against the parasite (that enhance the placental inflammation and impair pregnancy outcomes) and the innate immune sensing by the fetal trophoblast (that protect the fetus presumably through preserving placental function);
• The molecular wiring of innate immune sensing in trophoblasts links to vasoregulatory responses enabling alterations in cell motility and migration potentially impacting microcirculatory regulation in the placenta.

Puzzled by these observations we plan to investigate the pathophysiological relevance of trophoblast responses to malaria in two angles:

• As modifiers of placental blood spaces topology clarifying the unsolved issue of regulation of maternal blood microcirculation in the placenta during infection;
• Investigating whether placental perturbations induced by the malaria parasite restrain the responses of the affected fetus in post-natal life.