title: Mast cell-macrophage dynamics in modulation of dengue virus infection in skin.
abstract: Dengue virus (DENV) infection causes dengue fever, dengue haemorrhagic fever, or dengue shock syndrome. Mast cells have been speculated to play a role in DENV disease although their precise roles are unclear. In this study, we used mast cell-deficient Kit(W-sh/W-sh) mice to investigate the involvement of mast cells after intradermal DENV infection. An approximately two- to three-fold higher level of DENV NS3 antigen was detected at the skin inoculation site in DENV-infected Kit(W-sh/W-sh) mice than in DENV-infected wild-type (WT) mice (using a dose of 1 × 10(9) plaque-forming units/mouse). Moreover, as an indicator of heightened pathogenesis, a more prolonged bleeding time was observed in DENV-infected Kit(W-sh/W-sh) mice than in WT mice. Monocytes/macrophages are considered to be important targets for DENV infection, so we investigated the susceptibility and chemokine response of DENV-infected peritoneal macrophages from Kit(W-sh/W-sh) and WT mice both ex vivo and in vivo. There was a tendency for higher DENV infection and higher secretion of CCL2 (MCP-1) from peritoneal macrophages isolated from Kit(W-sh/W-sh) mice than those from WT mice. In vivo studies using intradermal inoculation of DENV showed about twofold higher levels of infiltrating macrophages and CCL2 (MCP-1) at the inoculation site in both mock control and DENV-inoculated Kit(W-sh/W-sh) mice than in corresponding WT mice. In summary, compared with WT mice, Kit(W-sh/W-sh) mice show enhanced DENV infection and macrophage infiltration at the skin inoculation site as well as increased DENV-associated bleeding time. The results indicate an intriguing interplay between mast cells and tissue macrophages to restrict DENV replication in the skin.
authors.affiliation: Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chu
authors.affiliation: Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan.|Centre of Infectious Disease and Signalling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Wan
authors.affiliation: Departments of Microbiology & Immunology and Paediatrics and Canadian Centre for Vaccinology, Dalhousie University, Halifax, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan.|Centre of Infectious Disease and Signalling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D003715:Dengue / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020365:RNA Helicases / Q000276:immunology / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000276:immunology* / Q000378:metabolism; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000914:Antibodies, Viral; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D020365:RNA Helicases; D012367:RNA, Viral; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C491768:Ccl2 protein, mouse; C503460:Ccl5 protein, mouse; C485433:Cxcl10 protein, mouse; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: KitW-sh/W-sh mice; dengue virus; macrophage; mast cell