title: Diabetic pregnancy activates the innate immune response through TLR5 or TLR1/2 on neonatal monocyte.
abstract: Diabetes mellitus (DM) during pregnancy causes congenital malformation, macrosomia, respiratory distress syndrome, and other abnormalities in neonates, but whether maternal DM affects the neonatal innate immune system is unknown. Therefore we aimed to reveal the influence of DM in pregnancy on the toll-like receptor (TLR)-mediated innate immune response in neonates. Cord blood was collected after full-term vaginal or cesarean delivery and classified into a DM group (n=8) and non-DM (control) group (n=7). Mononuclear cells were harvested from cord blood by using density gradient centrifugation, after which anti-CD14 magnetic beads were used to isolate monocytes from the mononuclear population. After monocytes were cultured with lipopolysaccharide (TLR4 ligand), flagellin (TLR5 ligand), Pam3CSK4 (TLR1/TLR2 ligand), zymosan (TLR2/TLR6 ligand), or macrophage-activating lipopeptide (TLR2/TLR6 ligand) for 12h, the cytokine levels (interleukin [IL]-8, IL-6, IL-1β, IL-10, tumor necrosis factor alpha and IL-12) in the culture supernatants were measured. Compared with the control group, the DM group had higher concentrations of IL-8 (P=0.01) and tumor necrosis factor alpha (P=0.02) after monocyte cultures were stimulated with Pam3CSK4 and higher concentrations of IL-8 (P=0.01) after flagellin treatment. In contrast, stimulation with lipopolysaccharide, zymosan, or macrophage-activating lipopeptide did not lead to any difference in cytokine profiles between the two groups. These data indicate that maternal DM induces excessive inflammatory activation in neonates via a TLR5- or TLR1/2-mediated innate immune response.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
authors.forename: Sakika
authors.initials: S
authors.lastname: Yanai
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan. Electronic address: m1155519@med.osaka-cu.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tokuhara
authors.affiliation: Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tachibana
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakashita
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Shintaku
authors.affiliation: Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Koyama
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000276:immunology*; D016209:Interleukin-8 / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009765:Obesity; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000276:immunology*; D051194:Toll-Like Receptor 1 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016209:Interleukin-8; C495342:TLR2 protein, human; C495346:TLR5 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051198:Toll-Like Receptor 5; D014409:Tumor Necrosis Factor-alpha
keywords: Cord blood; Gestational diabetes mellitus; Innate immunity; Monocyte; Toll-like receptor