Subcapsular sinus macrophages limit dissemination of West Nile virus particles after inoculation but are not essential for the development of West Nile virus-specific T cell responses

包膜下窦巨噬细胞限制了接种后西尼罗河病毒颗粒的传播,但对于西尼罗河病毒特异性 T 细胞反应的发展并非至关重要

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作者:Evandro R Winkelmann, Douglas G Widman, Jingya Xia, Alison J Johnson, Nico van Rooijen, Peter W Mason, Nigel Bourne, Gregg N Milligan

Abstract

Macrophages encounter flaviviruses early after injection by arthropod vectors. Using in vivo imaging of mice inoculated with firefly luciferase-expressing single-cycle flavivirus particles (FLUC-SCFV), we examined the initial dissemination of virus particles in the presence or absence of lymph node (LN)-resident macrophages. Higher luciferase activity, indicating higher SCFV gene expression, was detected in the footpad of macrophage-depleted mice after 24h post infection (hpi). Moreover, FLUC-SCFV particles disseminated to the spleen within 14 hpi in macrophage-depleted, but not control mice. Although macrophages presented SCFV to naïve T cells in vitro, depletion of subcapsular sinus (SCS) macrophages did not alter the magnitude or effector function of the WNV-specific CD8(+) T cell response. Together, these results indicate that SCS macrophages play a role in limiting the dissemination of SCFV early in infection but are not required for the generation of a polyfunctional WNV-specific CD8(+) T cell response in the draining LN.

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