- Title Information
- Title
- Survival & Acute Lung Injury in Neonatal Sepsis: Role of Checkpoint Protein Vista
- Type of Resource (primo)
- text_resources
- Abstract
- Sepsis is a dysregulated host response to an infection that can lead to life-threatening end organ failure. Sepsis mortality in neonates has not significantly improved despite the advance of neonatal critical care in general. Indirect acute lung injury (iALI), one manifestation of septic organ dysfunction, is thought to result from impaired barrier function of pulmonary microvasculature, allowing for neutrophil invasion. Immune checkpoint proteins (ICPs) have been identified in studies of neonatal and adult sepsis as key regulators of sepsis progression, improving both morbidity and mortality. V-Domain Ig Suppressor of T-Cell Activation (VISTA) is an ICP that protects against inflammation-induced tissue damage and mortality in adult murine sepsis. W hypothesized that VISTA improves mortality and morbidity due to iALI in neonates by suppressing neutrophil-induced edema and tissue damage. A cecal slurry model of septic challenge was performed on C57BL/6 and VISTA-gene knockout 5-7 days old pups. We determined in a survival study that VISTA confers no survival advantage in neonatal septic challenge. Further, measurement of lung wet-to-dry weights harvested 24-hours after performing cecal slurry showed no important morbidity improvement in VISTA expressing neonates. These results differ drastically from similar analysis in adult mice and suggest that VISTA functions differently in the neonatal immune system than in the adult. The neonatal immune system may have compensating redundant pathways not present in the adult which explain the lack of mortality in VISTA-deficient mice. Given that ICPs represent a potential target for precision sepsis therapies, future studies are needed to articulate the differences in the neonatal immune response to septic challenge
- Name
- Name Part
- Kwasnik, Matthew
- Role
- Role Term (marcrelator)
(authorityURI="http://id.loc.gov/vocabulary/relators", valueURI="http://id.loc.gov/vocabulary/relators/aut")
- Author
- Name
- Name Part
- Gray, Chyna
- Role
- Role Term (marcrelator)
(authorityURI="http://id.loc.gov/vocabulary/relators", valueURI="http://id.loc.gov/vocabulary/relators/aut")
- Author
- Name
- Name Part
- Ayala, Alfred
- Role
- Role Term (marcrelator)
(authorityURI="http://id.loc.gov/vocabulary/relators", valueURI="http://id.loc.gov/vocabulary/relators/aut")
- Author
- Name:
Corporate
- Name Part
- Brown University. Alpert Medical School. Scholarly Concentration Program. Translational Research in Medicine
- Role
- Role Term:
Text
- research program
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/")
- Topic
- sepsis
- Language
- Language Term:
Text (ISO639-2B)
- English
- Origin Information
- Date Created
(keyDate="yes", encoding="w3cdtf")
- 2024
- Note
(displayLabel="Scholarly concentration")
- Translational Research in Medicine
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use and reproduction
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