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Developmental expression of Toll-like receptors-2 and -4 in preterm baboon lung
Shanjana Awasthi1, Jodie Cropper, Kevin M Brown
1Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, 1110 N. Stonewall Avenue, Oklahoma City, OK 73117, USA. Shanjana-Awasthi@ouhsc.edu
Insights
Immune responses in preterm infants are developing. Lung Toll-like receptor (TLR) expression increases with fetal development but changes during infection, impacting host defense.
Area of Science:
- Immunology
- Neonatology
- Developmental Biology
Background:
- Preterm infants possess immature lung and immune systems, increasing susceptibility to respiratory infections.
- Toll-like receptors (TLRs) on immune cells are crucial for host defense, particularly in local lung immunity.
Purpose of the Study:
- To investigate the developmental expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in fetal baboon lung tissue.
- To examine how lung TLR expression is altered in preterm baboons experiencing natural bacterial or fungal infections.
Main Methods:
- Quantification of TLR2 and TLR4 messenger RNA (mRNA) and protein levels using Northern and Western blotting techniques.
- Analysis of lung tissue from fetal baboons at different gestational ages (125, 140, 175 days) and from naturally infected preterm baboons.
Main Results:
- TLR2 and TLR4 expression was significantly low at 125 and 140 days of gestation (dGA), reaching adult levels by 175 dGA.
- In infected baboons, TLR4 mRNA decreased, while TLR2 mRNA remained unchanged.
- Protein expression of both TLR2 and TLR4 increased in naturally infected baboons.
Conclusions:
- Lung TLR expression is developmentally regulated in fetal baboons.
- Respiratory infections in preterm infants alter lung TLR expression patterns, affecting the host's immune response.
Abstract:
Preterm babies are susceptible to respiratory infection due to immature lung and immune system. Immune cells express Toll-like receptors (TLRs), which may be important in local host defense of preterm infants. We studied the expression of TLR2 and TLR4 in lung tissues of fetal baboons delivered at 125, 140, and 175 days of gestation (dGA; term=185+/-2 days) and preterm baboons that became naturally infected with bacterial/fungal pathogens. The TLR-mRNA and protein were quantified by Northern and Western blotting, respectively. The expression of both TLRs was significantly low at 125 and 140dGA. At 175dGA, the levels reached equivalent to those in adult baboons. However, in naturally infected baboons, the TLR4-mRNA was reduced (p<0.05); TLR2-mRNA expression remained unaltered. The protein expression of both TLRs was found increased in naturally infected baboons. Our results suggest that the lung TLR expression is developmentally regulated and altered during respiratory infection in preterm babies.

