Plasmacytoid Dendritic Cell Depletion Modifies Foxp3+T Cell Homeostasis And The Clinical Course Of Bacterial Pneumonia In Mice
JOURNAL OF LEUKOCYTE BIOLOGY(2019)
摘要
Plasmacytoid dendritic cells (pDC) are critical to antiviral defense because of their high production of type I IFNs; less is known regarding their functions in bacterial infection. Moreover, pDC are involved in immunomodulation. A stable pool of regulatory T cells (Treg) is crucial for maintaining immune homeostasis. However, interactions between pDC and Treg regarding the regulation of Treg homeostasis are understudied. By using BDCA2-DTR mice as a systemic pDC depletion model, we identified increased steady-state numbers of FoxP3(+) T cells with an effector Treg-like phenotype in lungs, liver, and spleen tissues. During sublethal, pulmonary Klebsiella pneumoniae infection, pDC deficiency also elevated respiratory FoxP3(+) T cell numbers. Additionally, the improvement in acute pneumonia survival until day 5 post infection was accompanied by impaired proinflammatory cytokine production. In contrast, pDC-depleted mice exhibited a delayed clinical recovery during the post-acute phase. Therefore, we assume that pDC act as immunomodulators supporting the rapid onset of immune response in a proinflammatory manner and regulate inflammation or tissue regeneration in the post-acute phase. In summary, pDC assist in FoxP3(+) T cell homeostasis and the regulation of Klebsiella-pneumonia progression.
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关键词
bacterial infection, BDCA2-DTR mice, immunomodulation, inflammation, Klebsiella pneumoniae, regulatory T cells
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