title: Immune response to intrapharyngeal LPS in neonatal and juvenile mice.
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.
authors: 1 Eudowood Division of Pediatric Respiratory Sciences.
authors: Sharon A
authors: SA
authors: McGrath-Morrow
authors: Seakwoo
authors: S
authors: Lee
authors: Kevin
authors: K
authors: Gibbs
authors: Armando
authors: A
authors: Lopez
authors: Joseph M
authors: JM
authors: Collaco
authors: Enid
authors: E
authors: Neptune
authors: Mark J
authors: MJ
authors: Soloski
authors: Alan
authors: A
authors: Scott
authors: Franco
authors: F
authors: D'Alessio
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology*; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology; D018946:Chemokine CCL5 / Q000276:immunology; D054357:Chemokine CXCL10 / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D008070:Lipopolysaccharides; D016753:Interleukin-10
keywords: Escherichia coli LPS; acute lung injury; juvenile; neonate