Patients with idiopathic pulmonary fibrosis (IPF) can experience life-threatening episodes of acute worsening of their disease, termed acute exacerbation of IPF, which may be caused by bacterial and/or viral infections. The potential for regulatory T cells (Tregs) to limit disease progression in bacterially triggered fibrosis exacerbation has not been explored so far. In the current study, we show that the number of Tregs was significantly increased in mice with established AdTGF-β1-induced lung fibrosis and further increased in mice with pneumococcal infection-induced lung fibrosis exacerbation. Diphtheria toxin-induced depletion of Tregs significantly worsened infection-induced fibrosis exacerbation as determined by increased lung collagen deposition, lung histology, and elevated pulmonary Th1/Th2 cytokine levels. Conversely, IL-2 complex-induced Treg expansion in wild-type mice with established lung fibrosis completely inhibited pneumococcal infection-induced fibrosis exacerbation as efficaciously as antibiotic treatment while preserving lung antibacterial immunity in mice. Collectively, these findings demonstrate the efficacy of Tregs as "silencers," suppressing infection-induced exacerbation of lung fibrosis in mice, and their expansion may offer a novel adjunctive treatment to limit acute exacerbations in patients with IPF.
