Unmasking the role of mast cells in dengue

Abstract

Immune cells called mast cells can hinder rather than help the body's response to dengue virus, which suggests that mast cell products could be used as biomarkers to identify severe forms of the disease.

Keywords: Human; Mouse; Viruses; chymase; dengue virus; infectious disease; leukotrienes; mast cell; vascular leakage.

Conflict of interest statement

Competing interests:The authors declare that no competing interests exist.

Figures

Figure 1.

The response of mast cells to dengue virus can be beneficial or detrimental. When a mosquito injects dengue virus (brown hexagons) into the skin, the viruses are detected by specific antibodies (green) or unidentified receptors (blue) on the surface of resting (i.e., non-activated) mast cells. These can then trigger an anti-viral response (left) by releasing the contents of their granules (degranulation) and by upregulating intracellular anti-viral molecules (RIG-I and MDA5). The activated mast cells also secrete signaling molecules called chemokines, which recruit other immune cells including natural killer cells (NK), natural killer T cells (NKT) and T cells, which help to clear the virus. However, if local control mechanisms fail, the virus will enter the bloodstream and be carried to other organs (right). This activates the mast cells in these organs so that they undergo degranulation, releasing ready-made proteases such as chymase and tryptase, and synthesizing inflammatory mediators (leukotrienes and vascular endothelial cell growth factor [VEGF]). These increase the permeability of capillaries, leading to vascular leakage. Mast cells in these organs can also be activated by endogenous inflammatory mediators (such as C3a and C5a) that help the body to remove pathogens. Blocking mast cells (or their mediators) with drugs such as cromolyn, ketotifen and montelukast reduces pathogenic vascular leakage, but might also hamper viral clearance. Anti-mast cell therapy could thus be a double-edged sword.