ABSTRACT
Introduction: The induction of regulatory T cells (Tregs) is indicated as a potential therapeutic strategy in inflammatory lung diseases including, asthma, viral-induced pneumonia, viral-induced acute lung injury (ALI), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and SARSCoV- 2-induced ALI. We previously identified that components of the bacteria Streptococcus pneumoniae (T + P) are able to increase Tregs to suppress experimental allergic airways disease, however, this mechanism of suppression and therapy has not been examined in ALI. Methods: We established a murine model of ALI using aerosolized LPS (100 μg/ml) in BALB/c mice. ALI was measured by the presence of neutrophils in the airways up to 96 hours post-exposure, and Tregs and dendritic cells were assessed by flow cytometry. To assess the therapeutic of T + P in ALI and the mechanisms involved, the combination was administered prior to LPS exposure in the absence or presence of anti-CD25. Results: Treatment with T + P significantly reduced total airway inflammation and suppressed the neutrophil chemokine C-X-C motif chemokine ligand 1 (Cxcl1) compared to Saline+LPS alone in experimental ALI. The numbers of Tregs were reduced in experimental ALI model and were restored by T + P treatment. Depletion of Tregs with anti- CD25 confirmed that the suppressive effects of T + P on ALI was through the induction of Tregs. Conclusion: Treatment with S. pneumoniae components T + P suppresses neutrophilic inflammation in ALI through immunoregulatory mechanisms that involve Tregs and may be a novel treatment for ALI including in COVID-19.