Related Experiment Video
Updated: Nov 25, 2025
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
CD71+ Erythroid Cells in Human Neonates Exhibit Immunosuppressive Properties and Compromise Immune Response Against
Shokrollah Elahi1,2,3,4, Marco Antonio Vega-López5, Vladimir Herman-Miguel5
1School of Dentistry, University of Alberta, Edmonton, AB, Canada.
Insights
Newborns possess abundant immunosuppressive CD71+ erythroid cells (CECs) that regulate immune responses. Depleting these cells enhances resistance to infection, suggesting a novel mechanism for neonatal immunity.
Area of Science:
- Immunology
- Neonatal Biology
- Cell Biology
Background:
- Neonatal infection susceptibility is often attributed to immature immune systems.
- Physiological abundance of CD71+ erythroid cells (CECs), an immunosuppressive cell type, challenges this notion.
- CECs are present in newborn mice and human cord blood.
Purpose of the Study:
- To investigate the presence and function of CECs in human newborns.
- To determine the role of CECs in neonatal immune regulation and infection susceptibility.
Main Methods:
- Quantification of CECs in peripheral blood of human newborns and neonatal mice.
- Analysis of reactive oxygen species (ROS) production by CECs.
- Assessment of CECs' effect on cytokine production by monocytes and T cells.
- In vivo depletion of CECs in neonatal mice and subsequent infection challenge with Listeria monocytogenes.
Main Results:
- CECs are abundant in human newborns, declining by 4 weeks but remaining elevated up to 6 months.
- CD45+ CECs are a major source of ROS, with higher activity in spleen compared to bone marrow in mice.
- CECs suppress cytokine production by human monocytes and T cells.
- CEC depletion in mice increased effector immune cells and resistance to Listeria monocytogenes infection, improving survival.
Conclusions:
- CECs play a significant immunoregulatory role in newborns, contributing to their unique immune status.
- The immunosuppressive function of CECs may explain the generally mild or asymptomatic course of infections like COVID-19 in infants.
- CECs represent a novel target for modulating neonatal immunity.
Abstract:
Newborns are highly susceptible to infectious diseases. The underlying mechanism of neonatal infection susceptibility has generally been related to their under-developed immune system. Nevertheless, this notion has recently been challenged by the discovery of the physiological abundance of immunosuppressive erythroid precursors CD71+erythroid cells (CECs) in newborn mice and human cord blood. Here, as proof of concept, we show that these cells are also abundant in the peripheral blood of human newborns. Although their frequency appears to be more variable compared to their counterparts in mice, they rapidly decline by 4 weeks of age. However, their proportion remains significantly higher in infants up to six months of age compared to older infants. We found CD45 expressing CECs, as erythroid progenitors, were the prominent source of reactive oxygen species (ROS) production in both humans and mice. Interestingly, a higher proportion of CD45+CECs was observed in the spleen versus bone marrow of neonatal mice, which was associated with a higher ROS production by splenic CECs compared to their siblings in the bone marrow. CECs from human newborns suppressed cytokine production by CD14 monocytes and T cells, which was partially abrogated by apocynin in vitro. Moreover, the depletion of CECs in neonatal mice increased the number of activated effector immune cells in their spleen and liver, which rendered them more resistant to Listeria monocytogenes infection. This was evident by a significant reduction in the bacteria load in the spleen, liver and brain of treated-mice compared to the control group, which enhanced their survival rate. Our finding highlights the immunoregulatory processes mediated by CECs in newborns. Thus, such tightly regulated immune system in newborns/infants may explain one potential mechanism for the asymptomatic or mild COVID-19 infection in this population.
