Diana Hansen-Projects

Diana Hansen-Projects

Researcher: 

Projects

The role of inflammatory chemokines in the control of parasite densities and severe disease induction

The role of chemokines in malaria has only recently started to receive attention. Amongst these molecules, CXCL10 emerged as a biomarker associated with increased risk of cerebral malaria. Consistent with its role in humans, we found that CXCL10 neutralization alleviates brain inflammation and protects malaria-infected mice from cerebral malaria. Recent work revealed that apart from brain-specific effects, the absence of CXCL10 significantly reduces parasite burden. Our current work is investigating how CXCL10 modulates immune responses that control of parasitemia. This study will establish that inflammatory factors produced in response to malaria are the “cause” rather than a consequence of high parasite densities mediating severe disease in multiple organs.

 

Scientific figure showing nteractions between immune cells, cytokines and malaria parasites
Many types of immune cells and cytokines influence the inflammatory response to the malaria parasite, which contributes to the severity of disease, and has a role in cerebral malaria via effects on the brain microvasculature.

 

Development of B cell responses to malaria

Despite constant exposure to Plasmodium parasites, immunity to malaria takes many years to develop for individuals living in endemic areas. This form of protection is not sterilising but prevents clinical episodes by substantially reducing parasitaemia. Naturally acquired immunity is known to require antibody responses. Data from field studies suggest that antibodies to malarial antigens are rapidly lost in the absence of ongoing exposure though, suggesting a defect in B cell memory induction. Using infection models as well as field studies we are investigating the cellular and molecular processes underlying the slow and imperfect development of B cell-mediated immunity to malaria.

Scientific illustration
The same inflammatory processes that participate in the induction of severe malaria have a detrimental effect in the development of protective immunity by inhibiting the differentiation of T follicular helper cells required for effective antibody responses to infection.

 

Identification of effector mechanisms and antigenic targets of naturally acquired immunity to malaria

Antibodies against blood forms of the Plasmodium parasite are thought to play an important role in protective immunity. However, the specific antigens recognized by naturally acquired antibodies from protected individuals are unknown. Obtaining this information is essential to identify key antigens for new vaccine combinations and constitutes a critical validation step prior to further development.

Our team is using samples from field studies conducted in collaboration with scientists at the Eijkman Institute for Molecular Biology in Jakarta, Indonesia to identify immunological parameters and antigenic targets associated with reduced risk to re-infection and symptomatic disease. Multiplex cytometric arrays together with in vitro functional assays will reveal effector mechanisms by which antibodies control parasitemia.