title: Antibodies against nonstructural protein 1 protect mice from dengue virus-induced mast cell activation.
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.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chu
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Wan
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chien-Kuo
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Betty A
authors.initials: BA
authors.lastname: Wu-Hsieh
authors.affiliation: Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.|Department of Microbiology and Immunology and Canadian Center for Vaccinology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin