Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses
Journal
Scientific reports
Journal Volume
8
Journal Issue
1
Pages
12184
Date Issued
2018-08-15
Author(s)
Abstract
Enterovirus A71 (EV-A71) infection can induce encephalitis, which causes death or long-term neurological sequelae, especially in young children. Using a murine infection model, we searched for anti-EV-A71 agents, because effective therapies are not available to control fatal infection. In EV-A71-infected mice, treatment with the hematopoietic growth factor, Fms-like tyrosine-kinase 3 ligand (Flt3 ligand) before infection reduced the lethality and tissue viral loads. Flt3 ligand failed to enhance the production of type I interferons. Instead, Flt3 ligand boosted the numbers of dendritic cells and, particularly lymphocytes in infected organs with an expansion of spleen B cells, and resulted in an increased titer of virus-specific antibody with neutralizing activity in the serum. The protective effect of Flt3 ligand was abolished in B cell-deficient mice. Our findings revealed that Flt3 ligand administration promotes resistance to EV-A71 infection with enhanced B cell response in a mechanism rarely reported before.
SDGs
Other Subjects
CD135 antigen; flt3 ligand protein; FLT3 protein, human; membrane protein; neutralizing antibody; virus antigen; animal; B lymphocyte; C57BL mouse; cell line; disease model; Enterovirus; Enterovirus A; Enterovirus infection; female; human; immunology; male; metabolism; mortality; mouse; nonobese diabetic mouse; physiology; virology; virus load; virus replication; Animals; Antibodies, Neutralizing; Antigens, Viral; B-Lymphocytes; Cell Line; Disease Models, Animal; Enterovirus; Enterovirus A, Human; Enterovirus Infections; Female; fms-Like Tyrosine Kinase 3; Humans; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Viral Load; Virus Replication
Publisher
NATURE PUBLISHING GROUP
Type
journal article