How Dengue Gets Under Your Skin

The skin is an important site in the battle between dengue viruses and the immune system, study says.

AsianScientist (Mar. 18, 2015) – Immune cells that home specifically to the skin are activated during dengue virus infections, according to a study published in Science Translational Medicine. The finding suggests that triggering similar skin-homing properties could be important for developing a durable vaccine against dengue fever and related diseases.

Dengue virus (DENV) is transmitted by mosquitoes and can cause symptoms in humans that range from mild (fever, rashes) to life threatening (hemorrhagic fever, dengue shock syndrome). Although the number of cases of DENV infections are rising worldwide, there are currently no specific treatments or commercially available vaccines.

One reason for the lack of an effective therapy is that the immune response following DENV infection is poorly understood. For example, there are conflicting reports about the role of T cells in controlling DENV infection, with some groups reporting that T cells are essential and others claiming that activated T cells are linked to poorer outcomes.

In the present study, a team of researchers led by first author Dr. Laura Rivino from the Duke-NUS Graduate Medical School, have found that T cells that are specifically located to the skin play an important role in the body’s natural response to DENV.

Examining the blood of patients infected with DENV, they found that CD8+ T cells which recognized a dengue-specific peptide were activated, proliferating and expressing antiviral proteins such as interferon-γ and TNF-α. These dengue-specific T cells also expressed cutaneous lymphocyte-associated antigen (CLA), a marker associated with homing to the skin.

Interestingly, CLA was not expressed by activated T cells that were specific for another virus, human cytomegalovirus (HCMV). The researchers also found that CLA expression was three to six fold higher in dengue-specific T cells compared to non-dengue-specific T cells, suggesting that CLA expression is unique to dengue-specific T cells.

“In line with their expression of CLA, dengue-specific T cells are recruited to the skin as we find them in this site at high frequencies. Our data supports a role for skin-directed immunosurveillance against dengue and suggests that a vaccine targeting the dengue-immune response to the skin could have protective effects,” Rivino told Asian Scientist Magazine.

“Dengue virus enters the body through the skin by the bite of an infected mosquito. The finding that dengue-specific T cells that have anti-viral functions are populating this tissue suggests that these cells may have an important role in protection against re-infection.”

“It is interesting to note that the large majority of dengue patients form our patient cohort presented with skin rashes which may be linked to the presence of a local immune response to the virus,” she added.

The results could also explain why existing approaches to dengue vaccine design have not been successful.

“The current vaccine formulations are composed of structural components of the virus that are ideal targets for antibodies. We observe that most of the T cell targets are derived from non-structural proteins. However, non structural proteins are not part of the current vaccine formulations that are going through clinical trials. The implication is that these vaccines will poorly recapitulate the types of immune responses that underlie natural immunity to dengue found in recovered patients,” Rivino explained.

“It would be interesting and informative to look at the signatures of the T cells from individuals vaccinated with the different formulations that are currently undergoing clinical trial to understand which is able to elicit a T cell response similar to that elicited during natural infection.”

The article can be found at: Rivino et al. (2015) Virus-Specific T Lymphocytes Home to the Skin During Natural Dengue Infection.

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Copyright: Asian Scientist Magazine; Photo: Laura Rivino.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Rebecca did her PhD at the National University of Singapore where she studied how macrophages integrate multiple signals from the toll-like receptor system. She was formerly the editor-in-chief of Asian Scientist Magazine.

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