CD71⁺ erythroid suppressor cells impair adaptive immunity against Bordetella pertussis

Infant's immune system cannot control infection or respond to vaccination as efficiently as older individuals, a phenomenon that has been attributed to immunological immaturity. Recently, we challenged this notion and proposed the presence of actively immunosuppressive and physiologically enriched CD71⁺ erythroid cells in neonates. Here we utilized Bordetella pertussis, a common neonatal respiratory tract pathogen, as a proof of concept to investigate the role of these cells in adaptive immunity. We observed that CD71⁺ cells have distinctive immunosuppressive properties and prevent recruitment of immune cells to the mucosal site of infection. CD71⁺ cells ablation unleashed induction of B. pertussis-specific protective cytokines (IL-17 and IFN-γ) in the lungs and spleen upon re-infection or vaccination. We also found that CD71⁺ cells suppress systemic and mucosal B. pertussis-specific antibody responses. Enhanced antigen-specific adaptive immunity following CD71⁺ cells depletion increased resistance of mice to B. pertussis infection. Furthermore, we found that human cord blood CD71⁺ cells also suppress T and B cell functions in vitro. Collectively, these data provide important insight into the role of CD71⁺ erythroid cells in adaptive immunity. We anticipate our results will spark renewed investigation in modulating the function of these cells to enhance host defense to infections in newborns.