0 22

Cited 5 times in

Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation

 Sarah N. Cross  ;  Julie A. Potter  ;  Paulomi Aldo  ;  Ja Young Kwon  ;  Mary Pitruzzello  ;  Mancy Tong  ;  Seth Guller  ;  Carla V. Rothlin  ;  Gil Mor  ;  Vikki M. Abrahams 
 Journal of Immunology, Vol.199(8) : 2885-2895, 2017 
Journal Title
 Journal of Immunology 
Issue Date
Animals ; Cells, Cultured ; Chorioamnionitis ; Extraembryonic Membranes/immunology* ; Female ; Gammaherpesvirinae/immunology* ; Herpesviridae Infections/complications ; Herpesviridae Infections/immunology* ; Herpesvirus 2, Human/immunology* ; Humans ; Immunization ; Inflammasomes/metabolism* ; Intercellular Signaling Peptides and Proteins/metabolism ; Interleukin-1beta/metabolism ; Lipopolysaccharides/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pregnancy ; Premature Birth/etiology ; Premature Birth/immunology* ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism* ; Receptor Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/metabolism* ; c-Mer Tyrosine Kinase
Chorioamnionitis, premature rupture of fetal membranes (FMs), and subsequent preterm birth are associated with local infection and inflammation, particularly IL-1β production. Although bacterial infections are commonly identified, other microorganisms may play a role in the pathogenesis. Because viral pandemics, such as influenza, Ebola, and Zika, are becoming more common, and pregnant women are at increased risk for associated complications, this study evaluated the impact that viral infection had on human FM innate immune responses. This study shows that a herpes viral infection of FMs sensitizes the tissue to low levels of bacterial LPS, giving rise to an exaggerated IL-1β response. Using an ex vivo human FM explant system and an in vivo mouse model of pregnancy, we report that the mechanism by which this aggravated inflammation arises is through the inhibition of the TAM receptor, MERTK, and activation of the inflammasome. The TAM receptor ligand, growth arrest specific 6, re-establishes the normal FM response to LPS by restoring and augmenting TAM receptor and ligand expression, as well as by preventing the exacerbated IL-1β processing and secretion. These findings indicate a novel mechanism by which viruses alter normal FM immune responses to bacteria, potentially giving rise to adverse pregnancy outcomes.
Full Text
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
권자영(Kwon, Ja Young) ORCID logo https://orcid.org/0000-0003-3009-6325
RIS (EndNote)
XLS (Excel)
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.