Dengue fever, resulting from infection with the mosquito-borne dengue virus, can manifest as high fever, leaky blood vessels and hemorrhages throughout the body. This illness is commonly found in tropical countries such as Singapore. Now, an international team of researchers, including Katja Fink at the Singapore Immunology Network of A*STAR and the Novartis Institute for Tropical Diseases in Singapore, has reported that macrophages, a type of immune cell that engulfs foreign invaders, work within different organs to combat viral dissemination during infection.
In biopsies taken from infected individuals, the genetic material of the dengue virus is located within various types of immune cells, including macrophages. Fink and her co-workers wondered whether the macrophages were reservoirs for viral replication—as other groups have previously suggested—or whether the cells were instead involved in preventing viral expansion.
To answer this question, the researchers used a chemical to deplete macrophages in mice that they infected with dengue virus. Macrophage depletion initially led to reduced viral numbers in the blood and spleen, consistent with the postulated role of macrophages as being havens for viral replication. However, after a few days, viral loads bounced back, and ended up much higher than in normal mice. This suggests that the macrophages are important in controlling the amount of virus found in these organs.
When Fink and her co-workers injected dengue virus into the skin of the feet of the mice, they found the virus within macrophages in the nearby lymph nodes that drain lymph from those feet (Fig. 1). To get a clearer idea of the fate of this viral cargo, they specifically depleted macrophages in the draining lymph node. In this experiment, the researchers saw lower levels of virus in the lymph node and higher levels in the plasma. They therefore hypothesize that lymph node macrophages act as a sink to keep the virus out of the blood, perhaps to stop the virus from spreading throughout the body.
“The findings of our studies should revise the idea of macrophages as just being hosts for dengue replication and causing immunopathology,” says Fink. Instead, the data suggest that macrophages are important to fight the virus. Therapies aimed at targeting this cell population to enhance the production of anti-viral molecules could help reduce infection and disease.
Fink next plans on “identifying which soluble proteins are produced by macrophages and by other immune cell types that eventually add up to a highly inflammatory mixture” that leads to dengue fever symptoms in infected individuals.
The A*STAR-affiliated authors in this highlight are from the Singapore Immunology Network.