Immunology

Infants born to dengue immune mothers acquire maternal dengue antibodies. These antibodies, though initially protective, decline during the first year of life to levels thought to be disease enhancing, before reaching undetectable levels. We show that in this population, DENV-2 and DENV-4 almost exclusively cause disease in the presence of dengue antibody, despite infections occurring in others. We also observe serotype-specificity in the mean age of infant cases, consistent with differential waning of antibody to each serotype. These results highlight serotype-specificity in the way the immune response interacts with infection to cause disease. In addition, we show that the mean age of infant cases over time is informative about transmission in the whole population. Therefore, ongoing surveillance for dengue in infants could provide useful insights into dengue epidemiology, particularly after the introduction of a dengue vaccine targeting adults and older children.

Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population.

CLA + and to the mucosae?

Dengue virus infects hundreds of millions of people living in tropical countries every year. Transmitted via mosquito bites, the virus typically causes fever, but may also lead to potentially fatal organ failure. The development of mouse models of dengue virus infection could hasten an effective response to the disease, for which no specific treatments or licensed vaccines currently exist.

Now, an international team of researchers led by Katja Fink at the A*STAR Singapore Immunology Network has investigated small alterations in the normal mouse immune system to allow for the study of dengue virus infection, treatment and prevention.

Mice with a normal immune system are unable to be infected by dengue virus, which means that they cannot be used as model systems to understand dengue infection in humans. On the other hand, mice lacking normal interferon responses, which are generally required to fight viral infection, can be infected with the virus. But these mice do not mount a normal immune response, which does not make them very useful for learning about how the immune system reacts to dengue virus infection. Fink and colleagues reasoned that it would be highly beneficial to the field to have a mouse model that could be both infected with the virus and exhibit as normal an immune response as possible.

"Dendritic cells and macrophages are immune-cell types that had been previously shown in humans and mice to be potential targets for dengue virus infection, and both are key mediators of the immune response," explains Fink. "Therefore, we thought ablating interferon signaling in one or the other cell type could be sufficient to make mice susceptible to infection by the dengue virus," she says.