Innate immune response to LPS in airway epithelium is dependent on chronological age and antecedent exposures

Kinjal Maniar-Hew, Candice C. Clay, Edward M. Postlethwait, Michael J. Evans, Justin H. Fontaine, Lisa Miller

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The immune mechanisms for neonatal susceptibility to respiratory pathogens are poorly understood. Given that mucosal surfaces serve as a first line of host defense, we hypothesized that the innate immune response to infectious agents may be developmentally regulated in airway epithelium. To test this hypothesis, we determined whether the expression of IL-8 and IL-6 in airway epithelium after LPS exposure is dependent on chronological age. Tracheas from infant, juvenile, andadult rhesus monkeyswere first exposed to LPS ex vivo, and then processed for air-liquid interface primary airway epithelial cell cultures and secondary LPS treatment in vitro. Comparedwith adult cultures, infantandjuvenile cultures expressed significantly reduced concentrations of IL-8 after LPS treatment. IL-8 protein in cultures increased with animal age, whereas LPS-induced IL-6 protein was predominantly associated with juvenile cultures. Toll-like receptor (TLR) pathway RT-PCR arrays showed differential expressions of multiple mRNAs in infant cultures relative to adult cultures, including IL-1α, TLR10, and the peptidoglycan recognition protein PGLYRP2. To determine whether the age-dependent cytokine response to LPS is reflective of antecedent exposures, we assessed primary airway epithelial cell cultures established from juvenile monkeys housed in filtered air since birth. Filtered air-housed animal cultures exhibited LPS-induced IL-8 and IL-6 expression that was discordant with age-matched ambient air-housed animals. A single LPS aerosol in vivo also affected this cytokine profile. Cumulatively, our findings demonstrate that the innateimmuneresponse to LPS in airway epitheliumis variable with age, and may be modulated by previous environmental exposures.

Original languageEnglish (US)
Pages (from-to)710-720
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume49
Issue number5
DOIs
StatePublished - Nov 2013

Keywords

  • Airway epithelium
  • Cytokine
  • Infant
  • LPS
  • Toll-like receptor

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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