Immune response to intrapharyngeal LPS in neonatal and juvenile mice.
Am J Respir Cell Mol Biol
; 52(3): 323-31, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25068533
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Lipopolissacarídeos
/
Lesão Pulmonar Aguda
/
Pulmão
/
Animais Recém-Nascidos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article