Antibodies against nonstructural protein 1 protect mice from dengue virus-induced mast cell activation
Journal
Laboratory investigation; a journal of technical methods and pathology
Journal Volume
97
Journal Issue
5
Pages
602
Date Issued
2017-02-27
Author(s)
Chu, Ya-Ting
Wan, Shu-Wen
Chang, Yu-Chang
Anderson, Robert
Lin, Yee-Shin
Abstract
Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). DHF/DSS patients have been reported to have increased levels of urinary histamine, chymase, and tryptase, which are major granule-associated mediators from mast cells. Previous studies also showed that DENV-infected human mast cells induce production of proinflammatory cytokines and chemokines, suggesting a role played by mast cells in vascular perturbation as well as leukocyte recruitment. In this study, we show that DENV but not UV-inactivated DENV enhanced degranulation of mast cells and production of chemokines (MCP-1, RANTES, and IP-10) in a mouse model. We have previously shown that antibodies (Abs) against a modified DENV nonstructural protein 1 (NS1), designated DJ NS1, provide protection in mice against DENV challenge. In the present study, we investigate the effects of DJ NS1 Abs on mast cell-associated activities. We showed that administration of anti-DJ NS1 Abs into mice resulted in a reduction of mast cell degranulation and macrophage infiltration at local skin DENV infection sites. The production of DENV-induced chemokines (MCP-1, RANTES, and IP-10) and the percentages of tryptase-positive activated mast cells were also reduced by treatment with anti-DJ NS1 Abs. These results indicate that Abs against NS1 protein provide multiple therapeutic benefits, some of which involve modulating DENV-induced mast cell activation.Laboratory Investigation advance online publication, 27 February 2017; doi:10.1038/labinvest.2017.10.
SDGs
Other Subjects
antibody; chemokine; gamma interferon inducible protein 10; macrophage inflammatory protein 1alpha; macrophage inflammatory protein 1beta; monocyte chemotactic protein 1; nonstructural protein 1; RANTES; tryptase; animal cell; animal experiment; animal model; Article; cell activation; cell infiltration; controlled study; dengue; Dengue virus; enzyme linked immunosorbent assay; immunofluorescence; inoculation; macrophage; mast cell; mast cell degranulation; mouse; nonhuman; priority journal; virus inactivation; virus replication
Publisher
NATURE PUBLISHING GROUP
Type
journal article