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Dunsmore, Garett; Bozorgmehr, Najmeh; Delyea, Cole; Koleva, Petya; Namdar, Afshin; Elahi, Shokrollah
The Journal of immunology (1950), 09/2017, Volume: 199, Issue: 6Journal Article
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. 504: 158-162). We have used , 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 infection. CD71 cell ablation unleashed innate immune response and restored resistance to infection. In contrast, adoptive transfer of neonatal CD71 cells into adult recipients impaired their innate immune response to infection. Enhanced innate immune response to was characterized by increased production of protective cytokines IFN-γ, TNF-α, and IL-12, as well as recruitment of NK cells, CD11b , and CD11c cells in the lung. Neonatal and human cord blood CD71 cells express arginase II, and this enzymatic activity inhibits phagocytosis of in vitro. Thus, our study challenges the notion that neonatal infection susceptibility is due to immune cell-intrinsic defects and instead highlights active immune suppression mediated by abundant CD71 cells in the newborn. Our findings provide additional support for the novel theme in neonatal immunology that immunosuppression is essential to dampen robust immune responses in the neonate. We anticipate that our results will spark renewed investigation in modulating the function of these cells and developing novel strategies for enhancing host defense to infections in newborns.
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