Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions1,2,3,4,5,6,7. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71+ cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with l-arginine overrides immunosuppression. In addition, the ablation of CD71+ cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli8,9. However, CD71+ cell-mediated susceptibility to infection is counterbalanced by CD71+ cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition10,11. Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71+ cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these results will spark renewed investigation into the need for immunosuppression in neonates, as well as improved strategies for augmenting host defence in this vulnerable population.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
We thank D. Haslam, M. Hostetter, L. Muglia, J. Whitsett and C. Wilson for discussions, J. Mortensen for help with anaerobic cultures, and K. Eaton, C. Schray and the University of Michigan Unit for Laboratory Animal Medicine for providing germ-free mice. We thank the Mount Auburn OB-GYN associates, OB-GYN residents, and the University and Christ Hospital labour and delivery nursing staff for collecting cord blood, the Cell Processing and Manipulation Core for obtaining peripheral blood from adult donors, and the CCHMC Translational Research Trials Office for providing the regulatory and administrative support for studies with human cells. This research was supported by NIAID (R01AI087830 and R01AI100934) (S.S.W.) and NHLBI (R01HL103745) (A.F.S.). S.S.W. holds an Investigator in the Pathogenesis of Infectious Disease award from the Burroughs Wellcome Fund.