title: Maternal immune stimulation during pregnancy shapes the immunological phenotype of offspring.
abstract: Epidemiological studies have associated infection during pregnancy with increased risk of neurodevelopmental disorders in children, which is modeled in rodents by stimulating the immune system of pregnant dams with microorganisms or their mimics, such as poly(I:C) or LPS. In two prenatal mouse models, we show that in utero exposure of the fetus to cytokines/inflammatory mediators elicited by maternal immune stimulation with poly(I:C) yields offspring that exhibit a proinflammatory phenotype due to alterations in developmental programming of their immune system. Changes in the innate and adaptive immune elements of these pro-inflammatory offspring result in more robust responses following exposure to immune stimuli than those observed in control offspring from PBS-injected pregnant dams. In the first model, offspring from poly(I:C)-injected immunologically naïve dams showed heightened cellular and cytokine responses 4 h after injection of zymosan, a TLR2 agonist. In the second model, using dams with immunological memory, poly(I:C) injection during pregnancy produced offspring that showed preferential differentiation toward Th17 cell development, earlier onset of clinical symptoms of EAE, and more severe neurological deficits following immunization with MOG35-55. Such "fetal programming" in offspring from poly(I:C)-injected dams not only persists into neonatal and adult life, but also can have profound consequences on health and disease.
authors: UMDNJ-Graduate School of Biomedical Sciences, 185 South Orange Avenue, Newark, NJ 07101, USA.
authors: Mili
authors: M
authors: Mandal
authors: Robert
authors: R
authors: Donnelly
authors: Stella
authors: S
authors: Elkabes
authors: Pan
authors: P
authors: Zhang
authors: Dan
authors: D
authors: Davini
authors: Brian T
authors: BT
authors: David
authors: Nicholas M
authors: NM
authors: Ponzio
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D005260:Female; D055809:Illness Behavior / Q000502:physiology; D056747:Immunomodulation / Q000276:immunology*; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009035:Mothers; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage; D010446:Peptide Fragments / Q000008:administration & dosage; D011070:Poly I-C / Q000008:administration & dosage / Q000009:adverse effects; D011247:Pregnancy; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015054:Zymosan / Q000008:administration & dosage
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D015054:Zymosan; D011070:Poly I-C
keywords: Autoimmunity; Cytokines; EAE; Fetal programming; Immunopathology; Inflammation; Pregnancy; Th 17 cells