Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance

AL St. John, APS Rathore, H Yap… - Proceedings of the …, 2011 - National Acad Sciences
AL St. John, APS Rathore, H Yap, ML Ng, DD Metcalfe, SG Vasudevan, SN Abraham
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
A wealth of evidence supports the essential contributions of mast cells (MCs) to immune
defense against bacteria and parasites; however, the role of MCs in viral infections has not
been defined. We now report that rodent, monkey, and human MCs are able to detect
dengue virus (DENV), a lymphotropic, enveloped, single-stranded, positive-sense RNA virus
that results in MC activation and degranulation. We observe that the response of MCs to
DENV also involves the activation of antiviral intracellular host response pathways …
A wealth of evidence supports the essential contributions of mast cells (MCs) to immune defense against bacteria and parasites; however, the role of MCs in viral infections has not been defined. We now report that rodent, monkey, and human MCs are able to detect dengue virus (DENV), a lymphotropic, enveloped, single-stranded, positive-sense RNA virus that results in MC activation and degranulation. We observe that the response of MCs to DENV also involves the activation of antiviral intracellular host response pathways, melanoma differentiation-associated gene 5 (MDA5) and retinoic acid inducible gene 1 (RIG-I), and the de novo transcription of cytokines, including TNF-α and IFN-α, and chemokines, such as CCL5, CXCL12, and CX3CL1. This multifaceted response of MCs to DENV is consequential to the containment of DENV in vivo because, after s.c. infection, MC-deficient mice show increased viral burden within draining lymph nodes, which are known to be targeted organs during DENV spread, compared with MC-sufficient mice. This containment of DENV is linked to the MC-driven recruitment of natural killer and natural killer T cells into the infected skin. These findings support expanding the defined role of immunosurveillance by MCs to include viral pathogens.
National Acad Sciences