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Kerstin Luhn

Dr Kerstin Luhn

Research Fellow

Organisation

University of Oxford

Research summary

Lay

Dengue is with 100 million cases each year a major public health problem. The disease, caused by the mosquito-borne Dengue virus, is ranging from mild febrile illness to fatal haemorrhagic fever. The immune system rather than the virus seems to be responsible for the symptoms by producing exaggerated amounts of inflammatory mediators (cytokines), a phenomenon called immunopathology.

Immune responses and cytokine production are normally tightly regulated, e.g. by so called macrophages (MØ) and dendritic cells (DC). They are the first line of defence and adjust all subsequent immune responses and most importantly get infected by Dengue virus.

A key question is why Dengue involves immunopathology to a higher extend than other related virus infections like Influenza or Yellow Fever. We hypothesise that DENV infection is stimulating unique processes in the cells that finally lead to immunopathology. Therefore the aim of the study is to compare and understand processes in DC after Dengue and other viral stimulations. DC are infected with viruses in the laboratory and subsequently the cytokine release, virus production and other immunological parameters will be analysed. Triggered responses within the stimulated cells will be analysed on a molecular level to be able to gain a mechanistic insight in the Dengue pathology. Results will be confirmed using Dengue patient samples obtained from the Hospital for Tropical diseases in Ho Chi Minh City, Vietnam.

Information obtained by this study could have a major impact on human health. There is a significant necessity for basic and clinical research on immune responses in Dengue, especially on regulatory mechanisms as immunopathology is involved. Any treatment stimulating the immune response in an inadequate way could have a detrimental effect for the patients and increase disease severity. This study will contribute to our understanding of Dengue pathogenesis and therefore helps the design of future treatments and vaccines.

Grants awarded

Immune regulation in Dengue infection by macrophages and regulatory T cells

Scheme: Dorothy Hodgkin Fellowship

Dates: Oct 2008 - Apr 2013

Value: £399,996.78