Smit Joost J, Lindell Dennis M, Boon Louis, Kool Mirjam, Lambrecht Bart N, Lukacs Nicholas W
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
PLoS One. 2008 Mar 5;3(3):e1720. doi: 10.1371/journal.pone.0001720.
Respiratory syncytial virus (RSV) infects nearly all infants by age 2 and is a leading cause of bronchiolitis. RSV may employ several mechanisms to induce immune dysregulation, including dendritic cell (DC) modulation during the immune response to RSV.
Expansion of cDC and pDC by Flt3L treatment promoted an anti-viral response with reduced pathophysiology characterized by decreased airway hyperreactivity, reduced Th2 cytokines, increased Th1 cytokines, and a reduction in airway inflammation and mucus overexpression. These protective aspects of DC expansion could be completely reversed by depleting pDCs during the RSV infection. Expansion of DCs by Flt3L treatment enhanced in CD8+ T cell responses, which was reversed by depletion of pDC.
These results indicate that a balance between cDC and pDC in the lung and its lymph nodes is crucial for the outcome of a pulmonary infection. Increased pDC numbers induced by Flt3L treatment have a protective impact on the nature of the overall immune environment.
呼吸道合胞病毒（RSV）在2岁前几乎感染所有婴儿，是细支气管炎的主要病因。RSV可能采用多种机制诱导免疫失调，包括在对RSV的免疫反应过程中调节树突状细胞（DC）。
通过Flt3L治疗使cDC和pDC扩增，促进了抗病毒反应，病理生理学改变减轻，表现为气道高反应性降低、Th2细胞因子减少、Th1细胞因子增加以及气道炎症和黏液过度表达减少。在RSV感染期间通过消耗pDC，DC扩增的这些保护作用可完全逆转。通过Flt3L治疗使DC扩增增强了CD8+T细胞反应，这一作用通过消耗pDC而逆转。
这些结果表明，肺及其淋巴结中cDC和pDC之间的平衡对于肺部感染的结局至关重要。Flt3L治疗诱导的pDC数量增加对整体免疫环境的性质具有保护作用。
