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Sialic acid is a critical fetal defense against maternal complement attack
- Publication Year :
- 2018
- Publisher :
- American Society for Clinical Investigation, 2018.
-
Abstract
- The negatively charged sugar sialic acid (Sia) occupies the outermost position in the bulk of cell surface glycans. Lack of sialylated glycans due to genetic ablation of the Sia-activating enzyme CMP–sialic acid synthase (CMAS) resulted in embryonic lethality around day 9.5 post coitum (E9.5) in mice. Developmental failure was caused by complement activation on trophoblasts in Cmas(–/–) implants and was accompanied by infiltration of maternal neutrophils at the fetal-maternal interface, intrauterine growth restriction, impaired placental development, and a thickened Reichert’s membrane. This phenotype, which shared features with complement receptor 1-related protein Y (Crry) depletion, was rescued in E8.5 Cmas(–/–) mice upon injection of cobra venom factor, resulting in exhaustion of the maternal complement component C3. Here we show that Sia is dispensable for early development of the embryo proper but pivotal for fetal-maternal immune homeostasis during pregnancy, i.e., for protecting the allograft implant against attack by the maternal innate immune system. Finally, embryos devoid of cell surface sialylation suffered from malnutrition due to inadequate placentation as a secondary effect.
- Subjects :
- 0301 basic medicine
Complement receptor
Biology
03 medical and health sciences
chemistry.chemical_compound
Mice
Fetus
Pregnancy
Animals
Complement Activation
Maternal-Fetal Exchange
Mice, Knockout
Innate immune system
Glycobiology
Placentation
Embryo
General Medicine
Complement C3
N-Acetylneuraminic Acid
Cell biology
Complement system
Sialic acid
Receptors, Complement
Trophoblasts
carbohydrates (lipids)
030104 developmental biology
chemistry
embryonic structures
Receptors, Complement 3b
Female
Research Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....48718313740ed22770740fda5336ec65