Plasmacytoid dendritic cell depletion modifies FoxP3+ T cell homeostasis and the clinical course of bacterial pneumonia in mice.

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.