title: Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78.
abstract: The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9(-/-) knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78-treated TLR2/3/4/7/9(-/-) homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78-exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.
authors.affiliation: Department of Clinical Chemistry and Molecular Diagnostics, Philipps-University of Marburg, 35043 Marburg, Germany.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Conrad
authors.forename: Ruth
authors.initials: R
authors.lastname: Ferstl
authors.forename: René
authors.initials: R
authors.lastname: Teich
authors.forename: Stephanie
authors.initials: S
authors.lastname: Brand
authors.forename: Nicole
authors.initials: N
authors.lastname: Blümer
authors.forename: Ali O
authors.initials: AO
authors.lastname: Yildirim
authors.forename: Cecilia C
authors.initials: CC
authors.lastname: Patrascan
authors.forename: Anna
authors.initials: A
authors.lastname: Hanuszkiewicz
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Otto
authors.initials: O
authors.lastname: Holst
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Petra I
authors.initials: PI
authors.lastname: Pfefferle
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: Holger
authors.initials: H
authors.lastname: Garn
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
mesh_terms: D000150:Acinetobacter / Q000276:immunology*; D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D001249:Asthma / Q000517:prevention & control*; D004731:Endotoxins / Q000032:analysis; D005260:Female; D005333:Fetus / Q000276:immunology*; D007113:Immunity, Innate; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology*
chemical_list: D004731:Endotoxins; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D010047:Ovalbumin