Regulatory T cells facilitate Th17 responses to Bordetella pertussis and aid in resolution of whooping cough in mice.

Abstract

Abstract Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (Bp). The prolonged nature of whooping cough has been associated with delayed Th17 responses, which are essential to resolve the infection. Regulatory T cells (Treg) are historically immunosuppressive, but have recently been demonstrated to facilitate proper immune responses during certain infections and to occasionally adapt proinflammatory phenotypes. Because Treg and Th17 cells are considered “brothers in arms,” we evaluated the role of Tregs during immune response to B. pertussis. Here, we test the hypothesis that Tregs are crucial for generating a proinflammatory response that resolves whooping cough. We show that homeostatic lung Tregs acquire a highly proliferative Th17 phenotype during Bp infection in mice and that the frequency of this Th17-like Tresg (T17reg) population raises in parallel with Th17 influx and expansion at late phases of infection. Our data suggests that the frequency of lung T17reg may be modulated by levels of IFNa and IL-2 in the lung. Depleting Foxp3+ cells throughout Bp infection resulted in decreased MHC class II expression on dendritic and endothelial cells, suggesting reduced APC maturation. Additionally, Treg knockout lead to increased lung IL-2 levels (which may diminish Th17 differentiation/accumulation) and compromised IL-17 secretion. Moreover, infected mice lacking Treg had an increased Bp load in the lungs. Our data support Tregs facilitating and assisting Th17 immune responses to Bp to help resolve the infection.