Maternal endotoxin exposure attenuates allergic airway disease in infant rats.
Prenatal exposures to immunogenic stimuli, such as bacterial LPS, have shown to influence the neonatal immune system and lung function. However, no detailed analysis of the immunomodulatory effects of LPS on postnatal T helper cell differentiation has been performed. Using a rat model, we investigated the effect of prenatal LPS exposure on postnatal T cell differentiation and experimental allergic airway disease. Pregnant rats were injected with LPS on day 20 and 21 (term = 22 days). Some of the offspring were sensitized and challenged with ovalbumin. Positive control animals were placebo exposed to saline instead of LPS, whereas negative controls were sensitized with saline. Expression of T cell-related transcription factors and cytokines was quantified in the lung, and airway hyperresponsiveness was measured. Prenatal LPS exposure induced a T helper 1 (T(H)1) immune milieu in the offspring of rats [i.e., increased T-bet and T(H)1 cytokine expression while expression of T(H)2-associated transcription factors (GATA3 and STAT6) and cytokines was decreased]. Prenatal LPS exposure did not trigger T(H)17 cell differentiation in the offspring. Furthermore, prenatal LPS exposure reduced ovalbumin-induced (T(H)2-mediated) airway inflammation, eosinophilia, and airway responsiveness. Thus, in utero exposure to endotoxin promotes a T(H)1 immune environment, which suppresses the development of allergic airway disease later in life.
Cao
Lei
L
Lung Biology Research Group, Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto.
Wang
Jinxia
J
Zhu
Yingchun
Y
Tseu
Irene
I
Post
Martin
M
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000941:Antigens; D016207:Cytokines; D008070:Lipopolysaccharides; D010047:Ovalbumin