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Newborns are highly susceptible to infection. The underlying mechanism of neonatal infection susceptibility has generally been associated with neonatal immune cell immaturity. In this study, we challenged this notion and built upon our recent discovery that neonates are physiologically enriched with erythroid TER119+ CD71+ cells (Elahi et al. 2013. Nature 504: 158–162). We have used Bordetella pertussis, a common neonatal respiratory tract infection, as a proof of concept to investigate the role of these cells in newborns. We found that CD71+ cells have distinctive immune-suppressive properties and suppress innate immune responses against B. pertussis infection. CD71+ cell ablation unleashed innate immune response and restored resistance to B. pertussis infection. In contrast, adoptive transfer of neonatal CD71+ cells into adult recipients impaired their innate immune response to B. pertussis infection …