title: Chlamydia muridarum lung infection in infants alters hematopoietic cells to promote allergic airway disease in mice.
abstract: BACKGROUND
  Viral and bacterial respiratory tract infections in early-life are linked to the development of allergic airway inflammation and asthma. However, the mechanisms involved are not well understood. We have previously shown that neonatal and infant, but not adult, chlamydial lung infections in mice permanently alter inflammatory phenotype and physiology to increase the severity of allergic airway disease by increasing lung interleukin (IL)-13 expression, mucus hyper-secretion and airway hyper-responsiveness. This occurred through different mechanisms with infection at different ages. Neonatal infection suppressed inflammatory responses but enhanced systemic dendritic cell:T-cell IL-13 release and induced permanent alterations in lung structure (i.e., increased the size of alveoli). Infant infection enhanced inflammatory responses but had no effect on lung structure. Here we investigated the role of hematopoietic cells in these processes using bone marrow chimera studies.
  
  
  RESULTS
  Neonatal (<24-hours-old), infant (3-weeks-old) and adult (6-weeks-old) mice were infected with C. muridarum. Nine weeks after infection bone marrow was collected and transferred into recipient age-matched irradiated naïve mice. Allergic airway disease was induced (8 weeks after adoptive transfer) by sensitization and challenge with ovalbumin. Reconstitution of irradiated naïve mice with bone marrow from mice infected as neonates resulted in the suppression of the hallmark features of allergic airway disease including mucus hyper-secretion and airway hyper-responsiveness, which was associated with decreased IL-13 levels in the lung. In stark contrast, reconstitution with bone marrow from mice infected as infants increased the severity of allergic airway disease by increasing T helper type-2 cell cytokine release (IL-5 and IL-13), mucus hyper-secretion, airway hyper-responsiveness and IL-13 levels in the lung. Reconstitution with bone marrow from infected adult mice had no effects.
  
  
  CONCLUSIONS
  These results suggest that an infant chlamydial lung infection results in long lasting alterations in hematopoietic cells that increases the severity of allergic airway disease in later-life.
authors.affiliation: Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, Callaghan, Australia.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Starkey
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Kim
authors.forename: Emma L
authors.initials: EL
authors.lastname: Beckett
authors.forename: Heidi C
authors.initials: HC
authors.lastname: Schilter
authors.forename: Doris
authors.initials: D
authors.lastname: Shim
authors.forename: Ama-Tawiah
authors.initials: AT
authors.lastname: Essilfie
authors.forename: Duc H
authors.initials: DH
authors.lastname: Nguyen
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
authors.forename: Joerg
authors.initials: J
authors.lastname: Mattes
authors.forename: Charles R
authors.initials: CR
authors.lastname: Mackay
authors.forename: Jay C
authors.initials: JC
authors.lastname: Horvat
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002690:Chlamydia Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D023502:Chlamydia muridarum; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D018793:Interleukin-13 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000150:complications / Q000276:immunology* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5