Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection

In neonatal mice, susceptibility to infection is due to an enriched subset of arginase-2-expressing CD71 + erythroid cells, which suppresses the systemic activation of immune cells, thereby protecting neonates against aberrant inflammation triggered by colonization with commensal microbes. Explaining newborns' vulnerability to infection During the first few weeks after birth, infants are highly susceptible to disseminated infection. This vulnerability is commonly attributed to intrinsic defects of the neonates' immune cells, but this study presents evidence that host defences are in fact compromised by active immune suppression within the neonatal environment. Sing Sing Way and colleagues show that in neonate mice, an arginase-2-expressing CD71 + erythrocyte subset suppresses systemic immune cell activation, thereby protecting against harmful inflammation that might be triggered by colonization with the commensal microbes to which the newborn is suddenly exposed. This same suppression has the unfortunate consequence that resistance to infection is also reduced. 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 conditions 1 , 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 coli 8 , 9 . However, CD71 + cell-mediated susceptibility to infection is counterbalanced by CD71 + cell-mediated protection against aberrant immune cell activation in the intestine, where colo