title: Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior
abstract: Maternal infection during pregnancy is associated with adverse outcomes for the fetus, including postnatal cognitive disorders. However, the underlying mechanisms are obscure. We find that bacterial cell wall peptidoglycan (CW), a universal PAMP for TLR2, traverses the murine placenta into the developing fetal brain. In contrast to adults, CW-exposed fetal brains did not show any signs of inflammation or neuronal death. Instead, the neuronal transcription factor FoxG1 was induced, and neuroproliferation leading to a 50% greater density of neurons in the cortical plate was observed. Bacterial infection of pregnant dams, followed by antibiotic treatment, which releases CW, yielded the same result. Neuroproliferation required TLR2 and was recapitulated in vitro with fetal neuronal precursor cells and TLR2/6, but not TLR2/1, ligands. The fetal neuroproliferative response correlated with abnormal cognitive behavior in CW-exposed pups following birth. Thus, the bacterial CW-TLR2 signaling axis affects fetal neurodevelopment and may underlie postnatal cognitive disorders.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Humann
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Mann
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Geli
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Moresco
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ramahi
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Lip Nam
authors.initials: LN
authors.lastname: Loh
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Arden
authors.initials: A
authors.lastname: Farr
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Yunming
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Durick-Eder
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Fillon
authors.affiliation: Department of Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Smeyne
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: elaine.tuomanen@stjude.org.
authors.forename: Elaine I
authors.initials: EI
authors.lastname: Tuomanen
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000150:complications*; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000503:physiopathology*; D005260:Female; D008431:Maternal-Fetal Exchange; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010457:Peptidoglycan / Q000378:metabolism*; D011247:Pregnancy; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D010457:Peptidoglycan; D051195:Toll-Like Receptor 2