Dengue viral infections are one of the most rapidly emerging mosquito borne viral
infections in the world, resulting in a huge economic burden in affected countries.
Currently there is no licensed vaccine to prevent dengue, nor an effective specific drug
for its treatment. Severe forms of dengue infection is characterized by vascular leak
leading to shock and haemorrhage, which is thought to occur as a result of complex
interactions between the virus, host genetics and the immune system.
Innate like lymphoid cells (ILCs) are a recently identified population of haematopoietic
effector lymphoid cells, which are predominantly tissue resident. The ILC subtype that
predominantly produces type 2 cytokines (IL-4, IL-5 and IL-13) are known as ILC type
2 (ILC2s) and have shown to be important in the pathogenesis of atopic eczema and
allergic asthma. Elevated type 2 cytokines are present in the blood of individuals with
acute severe dengue suggesting that ILC2 could be a source. Although the source of
these cytokines was previously thought to be from Th2 cells, we found that dengue-
specific T cells are not the primary source of these cytokines in acute infection.
Preliminary investigations done by Graham Ogg’s lab in ILC2s in acute dengue
infection, showed that ILC2s are greatly expanded in patients with acute dengue
infection, when compared to healthy seronegative individuals, in whom ILC2s are
rarely detected in peripheral blood. In addition, the frequency of ILC2s negatively
correlated with platelet counts, which is a marker of disease severity.
It has been shown that monocytes and dendritic cells, are significantly more
permissive to infection with the dengue virus in the presence of IL-4 and IL-13. In acute
dengue infection, monocytes and dendritic cells have shown to be the main cell types
infected with the virus. In addition, studies on determining risk factors for
hospitalization due to dengue infection in a large cohort of individuals (n=1689) in Sri
Lanka done by Gathsaurie Malavige’s group, showed that both bronchial asthma and
allergic rhinitis were significantly associated with a higher risk. Collectively, these data
suggest that since ILC2s are greatly expanded during acute dengue infection and
since monocytes and dendritic cells are more permissive to infection in the presence
of type 2 cytokines, ILC2s could be playing a role in the pathogenesis of acute dengue.
By understanding the role of ILC2 in disease pathogenesis, we aim to identify new
targets for therapeutic intervention.