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Published on: April 16, 2013
TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells
Jeremy Anderson1,2, Georgia Bender1,2, Cao Minh Thang3
1Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
Insights
Preterm infants show similar Toll-like receptor (TLR) responses to bacterial and viral agonists compared to term infants. Despite this, preterm infants remain more susceptible to infections, indicating other factors may be involved.
Area of Science:
- Immunology
- Neonatal Research
- Infectious Diseases
Background:
- Preterm infants exhibit increased susceptibility to severe infections compared to full-term infants.
- Differences in pathogen response, particularly Toll-like receptor (TLR) pathways, may contribute to this vulnerability.
- Limited data exists on viral TLR responses in preterm infants, despite known alterations in bacterial TLR responses.
Purpose of the Study:
- To investigate and compare the cellular and cytokine responses to bacterial and viral Toll-like receptor (TLR) agonists in preterm infants, term infants, and adults.
- To determine if differences in TLR-mediated immune responses contribute to the increased susceptibility of preterm infants to infections.
Main Methods:
- Cord blood mononuclear cells (CBMCs) from preterm infants, term infants, and adults were stimulated with agonists for TLR2, TLR3, TLR4, TLR7/8, and TLR9.
- Cell-specific NF-κB activation (inflammatory marker) was measured using intracellular flow cytometry.
- Cytokine responses were quantified using multiplex assays.
Main Results:
- Preterm and term infants displayed similar baseline TLR expression.
- Preterm infants showed increased monocyte activation with lipoteichoic acid (LTA) stimulation, but no other significant differences in NF-κB activation or cytokine responses were observed compared to term infants.
- Adults produced higher levels of IFN-α compared to infants after R848 stimulation, and term infants showed a stronger correlation between NF-κB and cytokine responses post-poly I:C and R848 stimulation.
Conclusions:
- Preterm and term infants possess a comparable capacity to respond to bacterial and viral TLR agonists.
- The similar TLR-mediated immune responses suggest that other immunological factors may underlie the increased infection susceptibility in preterm infants.
- Further research is needed to identify these factors and develop targeted interventions for vulnerable preterm populations.
Abstract:
Preterm infants are more susceptible to severe bacterial and viral infectious diseases than their full-term counterparts. A major contributor to this increased susceptibility may be due to differences in their ability to respond to pathogens. While studies have demonstrated altered bacterial Toll-like receptor (TLR) responses, there is limited data on viral TLR responses in preterm infants. In this study, cord blood mononuclear cells (CBMCs) from 10 moderately preterm (30.4-34.1 wGA), 10 term (37-39.5 wGA) infants, and 5 adults were stimulated with TLR2 (lipoteichoic acid), TLR3 (poly I:C), TLR4 (lipopolysaccharide), TLR7/8 (R848), and TLR9 (CpG-ODN 2216) agonists. Following stimulation, the cellular response was measured by intracellular flow cytometry to detect cell-specific NF-κB (as a marker of the inflammatory response), and multiplex assays were used to measure the cytokine response. This study found that preterm and term infants exhibit very similar baseline TLR expression. In response to both bacterial and viral TLR agonists comparing cell-specific NF-κB activation, preterm infants exhibited increased monocyte activation following LTA stimulation; however, no other differences were observed. Similarly, no difference in cytokine response was observed following stimulation with TLRs. However, a stronger correlation between NF-κB activation and cytokine responses was observed in term infants following poly I:C and R848 stimulation compared to preterm infants. In contrast, despite similar TLR expression, adults produced higher levels of IFN-α following R848 stimulation compared to preterm and term infants. These findings suggest preterm and term infants have a similar capacity to respond to both bacterial and viral TLR agonists. As preterm infants are more likely to develop severe infections, further research is required to determine the immunological factors that may be driving this and develop better interventions for this highly vulnerable group.
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