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A new unexpected twist in newborn immunity

Nature Medicine volume 20, pages 22–23 (2014)Cite this article

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Becky Adkins

In the latter part of the twentieth century, neonates were often referred to as immunodeficient, but research over the past 15 years has shown that neonatal immune responses defy this simple categorization. Neonates actually seem to embody the ultimate diversity in immune responsiveness, with responses ranging from very weak to very strong. Although robust responses can be observed, they are the exception, and often responses are weak and associated with poor vaccine outcomes and extreme susceptibility to infection. Understanding the cellular and molecular regulation of the poorly protective responses in neonates is a major challenge, and a better knowledge of the underlying immune mechanisms will allow the development of interventional strategies for enhancing neonatal immune responses in all settings. There is mounting evidence that the reduced responsiveness may be attributed to multiple factors, including developmentally regulated epigenetic processes2, negative regulators in plasma3 and the preferential development of T regulatory cells in early life relative to adulthood4. A recent paper by Elahi et al.1 adds another important negative regulatory mechanism by showing that both neonatal mouse spleen and human umbilical cord blood contain high proportions of CD71+ erythroid-lineage cells with immune-suppressive properties. Small numbers of phenotypically similar cells were also detected in adult mice and humans; however, the adult mouse CD71+ cells did not show immunosuppressive properties, suggesting that the negative regulatory function of this population may be specific to early development. Depletion of these cells led to enhanced innate responses of mouse neonatal cells to Listeria monocytogenes in vitro and increased resistance to bacterial growth in mouse neonates in vivo. Because the suppressive effects of these cells arose from their expression of arginase-2 and, strikingly, supplementation with arginine overcame immune suppression by these cells in vitro, transient arginine supplementation may be clinically effective in infants to potentially boost resistance during acute infection and enhance responses to inert vaccines. Interestingly, these CD71+ erythroid cells seem to be protective against inflammation during commensal colonization after birth, which sheds light into how neonates avoid excessive inflammation that could negatively affect normal postnatal development.

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Competing interests

O.L. has consulted for GlaxoSmithKline and MedImmune regarding development of immunomodulatory agents to prevent early-life infection. The other authors declare no conflict of interest.

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A new unexpected twist in newborn immunity. Nat Med 20, 22–23 (2014). https://doi.org/10.1038/nm.3448

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