Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B cell responses

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.

Deficiency of IL-20 receptor subunit A decreases enterovirus A71 lethality of mice with enhanced M1 macrophage polarization and cytokine

“…Previous reports of IL-20RA cytokines mostly focused on T cells to show that IL-19 or IL-20 can increase IL-10 and/or decrease IFN-γ to induce T cell polorazation toward a Th2 pro le [19][20][21]. We previously found that T cell responses, especially the Th2 response, promote the production of antibodies, which protect mice from EV-A71 infection [45][46][47], and that the Th2 cytokine IL-6 decreases EV-A71 lethality of mice [30], showing the protective role of Th2 response in EV-A71 infeciton of mice. In the present study, we focus on macrophages, as more abundant macrophages express the protective cytokine, IFN-γ, than T cells in infected IL-20RA −/− mice.…”