Fetal-derived activated CD83+ γδ T cells expand in preterm infants with sepsis.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE245131 | GEO | 2024/05/08
REPOSITORIES: GEO
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Project description:Background: Neonatal infection and sepsis are common for preterm infants due to their immature immune system. Early diagnosis is important for effective treatment but few early markers of systemic and neuro-inflammatory responses in neonates are known. We hypothesized that systemic infection with Gram-positive Staphylococcus epidermidis (SE) induces acute changes to proteins in plasma and cerebrospinal fluid (CSF), potentially affecting the immature brain of preterm neonates. Methods: Using preterm pigs as model for preterm infants, plasma and CSF samples were collected up to 24 h after SE infection and investigated by untargeted mass spectrometry (MS)-based proteomics. Selected differential proteins were further studied in vitro assays. Results: The clinical signs of sepsis and neuroinflammation in SE-infected piglets were associated with changes in multiple CSF and plasma proteins. Eight plasma proteins, including APOA4, haptoglobin, MBL1, vWF, LBP and sCD14, were affected already 6 h after infection. Likewise, acute phase reactants, including complement components, showed a time-dependent activation pattern after infection. Feeding bovine colostrum reduced the sepsis-related change in clinical parameters as well as plasma proteins. Neuroinflammation-related neuropeptide Y (NPY), IL-18 and MMP-14 showed distinct changes in the CSF and several brain regions (prefrontal cortex, PVWM, hippocampus) 24 h after infection. These changes were verified in TLR2 agonist-challenged primary microglia cells, where exogenous NPY suppressed the inflammatory response. Conclusion: Systemic infection with Gram-positive SE induces inflammation with rapid proteome changes in plasma and CSF in preterm newborn pigs. The observed early markers of sepsis and neuroinflammation in preterm pigs may serve as novel biomarkers for sepsis in preterm infants.
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Project description:Neonates manifest a unique host response to sepsis even among other children. Preterm neonates may experience sepsis soon after birth or during often protracted birth hospitalizations as they attain physiologic maturity. We examined the transcriptome using genome-wide expression profiling on prospectively collected peripheral blood samples from infants evaluated for sepsis within 24 hours after clinical presentation. Simultaneous plasma samples were examined for alterations in inflammatory mediators. Group designation (sepsis or uninfected) was determined retrospectively based on clinical exam and laboratory results over the next 72 hours from the time of evaluation. Unsupervised analysis showed the major node of separation between groups was timing of sepsis episode relative to birth (early, <3 days or late, >3 days). Principal component analyses revealed significant differences between patients with early or late sepsis despite the presence of similar key immunologic pathway aberrations in both groups. Unique to neonates, the uninfected state and host response to sepsis is significantly affected by timing relative to birth. Future therapeutic approaches may need to be tailored to the timing of the infectious event based on post-natal age.
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