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Protection against maternal infection-associated fetal growth restriction: proof-of-concept with a microbial-derived immunomodulator.
- Source :
-
Mucosal immunology [Mucosal Immunol] 2017 May; Vol. 10 (3), pp. 789-801. Date of Electronic Publication: 2016 Oct 19. - Publication Year :
- 2017
-
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.
- Subjects :
- Abortion, Spontaneous etiology
Abortion, Spontaneous prevention & control
Animals
Bacterial Infections complications
Disease Models, Animal
Down-Regulation
Female
Fetal Development
Humans
Inflammation Mediators metabolism
Lipopolysaccharides immunology
Male
Mice
Mice, Inbred BALB C
Orthomyxoviridae Infections complications
Pregnancy
Prenatal Exposure Delayed Effects prevention & control
Proof of Concept Study
Abortion, Spontaneous immunology
Antigens, Bacterial immunology
Bacterial Infections immunology
Immunologic Factors immunology
Influenza A virus immunology
Orthomyxoviridae Infections immunology
Prenatal Exposure Delayed Effects immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 27759021
- Full Text :
- https://doi.org/10.1038/mi.2016.85