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|Title:||Protection against maternal infection-associated fetal growth restriction: proof-of-concept with a microbial-derived immunomodulator|
|Citation:||Mucosal Immunology, 2017; 10(3):789-801|
|Publisher:||Nature Publishing Group|
|N M Scott, J F Lauzon-Joset, A C Jones, K T Mincham, N M Troy, J Leffler, M Serralha, S L Prescott, S A Robertson, C Pasquali, A Bosco, P G Holt and D H Strickland|
|Abstract:||Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Using mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial lipopolysaccharide or influenza. Focusing on LPS exposure, we demonstrate that the key molecular indices of maternal inflammatory stress, notably high levels of RANTES, MIP-1α, CCL2, KC, and G-CSF (granulocyte colony-stimulating factor) in gestational tissues/serum, are abrogated by OM85 pretreatment. Systems-level analyses conducted in parallel using RNASeq revealed that OM85 pretreatment selectively tunes LPS-induced activation in maternal gestational tissues for attenuated expression of TNF, IL1, and IFNG-driven proinflammatory networks, without constraining Type1-IFN-associated networks central to first-line antimicrobial defense. This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress, without compromising capacity for efficient pathogen eradication, represents an achievable therapeutic goal.Mucosal Immunology advance online publication 19 October 2016. doi:10.1038/mi.2016.85.|
|Keywords:||Animals; Mice, Inbred BALB C; Humans; Mice; Influenza A virus; Bacterial Infections; Orthomyxoviridae Infections; Abortion, Spontaneous; Prenatal Exposure Delayed Effects; Disease Models, Animal; Lipopolysaccharides; Inflammation Mediators; Immunologic Factors; Antigens, Bacterial; Down-Regulation; Fetal Development; Pregnancy; Female; Male; Proof of Concept Study|
|Rights:||© 2017 Society for Mucosal Immunology|
|Appears in Collections:||Biochemistry publications|
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