Dr Kerstin Luhn is investigating the effect of Dengue virus infection on innate immune cells to understand why Dengue, unlike other viral infections, is associated with high levels of immunopathology. An in vitro Dengue model is used and results are confirmed with Dengue patient samples from a cohort in Vietnam.
Dengue is with about 100 million cases each year a major public health problem in the tropics. This research aims to understand how the Dengue virus interacts with the innate immune response. Results are relevant for the design of a future anti-viral treatment or vaccine that are currently not available.
Research in Medicine needs to ultimately translate into better treatment of patients. Researchers at the Nuffield Department of Medicine, University of Oxford, collaborate to develop better care and improved preventive measures. Findings in the laboratory are translated into changes in clinical practice, from Bench to Bedside.
Q: What is Dengue infection?
KL: Dengue is, with about 100 million cases each year, a major public health problem in the tropical and sub tropical areas of the world. It is caused by any of the four slightly different sub types of the Dengue virus, and the virus actually gets transmitted by mosquitoes. The severity of the disease can range from the relatively mild Dengue fever, with a high fever and debilitating muscle and joint pain and nausea, to the more severe forms like Dengue Hemorrhagic Fever and Dengue shock syndrome. Patients suffering from the more severe forms do, on top of the normal symptoms, develop quite severe oedema or bleedings due to leaky blood vessels. Infants, children as well as adults can be diagnosed with Dengue but it is quite striking that the most severe forms of the disease are mostly affecting children. Although Dengue is such a big problem, in the mean time nearly half of the world’s population is living at risk of infection, there is still no vaccine available and we also don’t have any anti-viral drugs for treatment.
Q: What is the effect of Dengue on our innate immune system?
KL: The innate immune system is a key component of our body’s immune response. It is the first line of defence and it senses incoming pathogens and then sets the stage for all subsequent immune responses. It has great regulatory potential. It’s very important in Dengue because the virus infects innate immune cells and replicates in them. On top of this it is a bit of a special situation for Dengue because there is a growing body of evidence that the immune system itself, rather than the virus, is causing the symptoms. So this phenomenon is called immunopathology. We are now trying to investigate how the virus is interacting with the innate immune cells so we are looking at very early molecular events in innate immune cells upon Dengue virus encounter. Our aim is to understand how and actually into which direction the virus is trying to push the immune response. So that patients with Dengue actually finally end up with immunopathology in contrast to patients with a lot of other viral infections.
Q: And could this research lead to a vaccine or better treatment?
KL: A lot of different factors are actually important or play a role in the outcome of the Dengue infection, for example the genetic outfit of the host or the virulence of the infecting viral strain. But most notably the immune response seems to be responsible. By stimulating the immune response in an inappropriate way using a vaccine the outcome of the subsequent Dengue infection could even be worse so we have to be really careful with this. Therefore a basic understanding of immune processes in Dengue is vital for the development of a vaccine and also for the identification of a new drug targets. Our work has the potential to provide key information regarding these processes.
Q: What are the most important lines of research that have developed over the past five or ten years?
KL: It has been quite important to the field that Dengue has finally been recognised as an important and re-emerging disease; case numbers are dramatically on the rise. There have been suggestions that due to global warming the geographical distribution of the mosquito might increase and hence the Dengue prevalence. But these facts have broadly been acknowledged by now. In addition the field has been hampered for a long time by the lack of suitable model systems. Some studies into this improved the situation enormously now allowing research into diverse directions and we are now able to address a much broader range of questions.
Q: How does your research fit into translational medicine within the department?
KL: I think our work fits in quite well with work that is done by other groups in the department. For example we are collaborating with Professors Cameron Simmons and Jeremy Farrar at the Oxford University Clinical Research Unit at Ho Chi Minh City in Vietnam. Through this collaboration we have access to Dengue patient samples that help us to confirm the results that we obtained in the laboratory. We can then use those results; they can be translated and actually used for the design of potential new drugs or a vaccine.