Purpose: By dampening the immune response, Tregs may have a negative effect, contributing to persistence of infection in some cases. However, depletion of Tregs in some models has resulted in damaging immunopathology, autoimmunity, and graft rejection. Our lab proposed to study the role of Tregs in the context of chronic mycoplasma infection in a mouse model. We hypothesized that depletion of Tregs would cause more severe disease, but would also result in increased clearance of the mycoplasma.
Methods: Balb/c mice were administered an anti-CD25 antibody to deplete Tregs (defined as CD4+CD25+FoxP3+) or PBS control. Mice were then infected intranasally with Mycoplasma pulmonis or broth control. Mice were weighed every other day, and then sacrificed at 14 days post-infection. Lungs were harvested, visually scored for the presence of lesions, and processed for flow cytometry staining or for counts of colony forming units (CFU). In addition, serum was collected and ELISA’s run for immunoglobulin levels.
Results: Mice that were Treg-depleted and infected lost significantly more weight compared to mice that were only infected, only Treg depleted, or neither (negative control). Lungs of Treg-depleted mice showed significantly more lesions compared to mice that were infected only. Serum levels of IgG, IgM, and IgA were all significantly higher in Treg-depleted and infected mice compared to mice that were infected only. Despite drastic differences in disease severity, no difference in lung CFU counts was observed at any time point.
Conclusions: In keeping with our hypothesis, depletion of Tregs resulted in increased severity of disease in infected mice, demonstrating that Tregs are important in suppressing damaging inflammatory responses during mycoplasma respiratory disease. However, in contrast to our hypothesis, Tregs played no role in persistence of infection.