title: Innate immune response to LPS in airway epithelium is dependent on chronological age and antecedent exposures.
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, and adult rhesus monkeys were first exposed to LPS ex vivo, and then processed for air-liquid interface primary airway epithelial cell cultures and secondary LPS treatment in vitro. Compared with adult cultures, infant and juvenile 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 innate immune response to LPS in airway epithelium is variable with age, and may be modulated by previous environmental exposures.
authors.affiliation: 1 California National Primate Research Center and Center for Comparative Respiratory Biology and Medicine, and.
authors.forename: Kinjal
authors.initials: K
authors.lastname: Maniar-Hew
authors.forename: Candice C
authors.initials: CC
authors.lastname: Clay
authors.forename: Edward M
authors.initials: EM
authors.lastname: Postlethwait
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Evans
authors.forename: Justin H
authors.initials: JH
authors.lastname: Fontaine
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Miller
mesh_terms: D000336:Aerosols; D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology; D046509:Tissue Culture Techniques; D051193:Toll-Like Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D000336:Aerosols; D002352:Carrier Proteins; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051193:Toll-Like Receptors; C433788:lipopolysaccharide, E. coli O26-B6; C118897:peptidoglycan recognition protein