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Updated: Apr 26, 2026
The Utilization of Oropharyngeal Intratracheal PAMP Administration and Bronchoalveolar Lavage to Evaluate the Host Immune Response in Mice
Published on: April 2, 2014
Immune response to intrapharyngeal LPS in neonatal and juvenile mice
Sharon A McGrath-Morrow1, Seakwoo Lee, Kevin Gibbs
11 Eudowood Division of Pediatric Respiratory Sciences.
Insights
Neonates exhibit a weaker immune response to lung injury, with fewer regulatory T cells (Tregs). Supplementing neonatal mice with adult Tregs improved their recovery from acute lung injury (ALI).
Area of Science:
- Immunology
- Neonatal research
- Respiratory medicine
Background:
- Neonates and infants face higher risks of severe lower respiratory tract illnesses.
- Understanding age-related immune responses is crucial for treating acute lung injury (ALI).
Purpose of the Study:
- To investigate age-dependent cellular immune responses to acute lung injury (ALI) in neonatal versus juvenile mice.
- To explore the role of T regulatory cells (Tregs) in neonatal ALI.
Main Methods:
- Administered Escherichia coli lipopolysaccharide (LPS) via intrapharyngeal aspiration to neonatal and juvenile mice.
- Analyzed lung cells using flow cytometry and quantified cytokine/chemokine mRNA.
- Performed lung morphometry and injury scoring; utilized adoptive transfer of Tregs in neonatal mice.
Main Results:
- Neonatal mice showed a predominant M2 monocyte phenotype and slower inflammation resolution compared to juveniles.
- Neonatal lungs had lower mRNA levels of key inflammatory mediators (CCL2, CCL5, CXCL10, IL-10) post-LPS.
- Neonatal mice lacked an increase in airway Tregs after LPS exposure, unlike juveniles; Treg transfer improved outcomes.
Conclusions:
- Neonatal immune responses to LPS-induced ALI reveal distinct vulnerabilities, particularly a deficiency in airway Tregs.
- Age-related differences in Treg function are critical in early postnatal development and ALI.
- Adoptive transfer of Tregs offers a potential therapeutic strategy for neonatal ALI.
Abstract:
Neonates and infants have a higher morbidity and mortality associated with lower respiratory tract illnesses compared with older children. To identify age-related and longitudinal differences in the cellular immune response to acute lung injury (ALI), neonatal and juvenile mice were given Escherichia coli LPS using a novel, minimally invasive aspiration technique. Neonatal and juvenile mice received between 3.75 and 7.5 mg/kg LPS by intrapharyngeal aspiration. Airway and lung cells were isolated and characterized by flow cytometry, cytokine/chemokine mRNA expression from lung homogenates was quantified, and lung morphometry and injury scores were performed. LPS-treated neonatal mice underwent adoptive transfer with adult T regulatory cells (Tregs). After LPS aspiration, lung monocytes isolated from neonatal mice had a predominant M2 phenotype, whereas lung monocytes from juvenile mice displayed a mixed M1/M2 phenotype. At 72 hours after LPS exposure, neonatal lungs were slower to resolve inflammation and expressed lower mRNA levels of CCL2, CCL5, CXCL10, and IL-10. Juvenile, but not neonatal, mice demonstrated a significant increase in airway Tregs after LPS exposure. Adoptive transfer of adult Tregs into LPS-challenged neonatal mice resulted in reduced lung inflammation and improved weight gain. These findings underscore several vulnerabilities in the neonatal immune response to LPS-induced ALI. Most striking was the deficiency in airway Tregs after LPS aspiration. Adoptive transfer of adult Tregs mitigated LPS-induced ALI in neonatal mice, highlighting the importance of age-related differences in Tregs and their response to ALI during early postnatal development.
