Transcriptome network analysis links perinatal Staphylococcus epidermidis infection to microglia reprogramming in the immature hippocampus

Giacomo Gravina, Maryam Ardalan, Tetyana Chumak, Halfdan Rydbeck, Xiaoyang Wang, Carl Joakim Ek, Carina Mallard*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

6 Citations (Scopus)
5 Downloads (Pure)

Abstract

Staphylococcus epidermidis (S. epidermidis) is the most common nosocomial pathogen in preterm infants and associated with increased risk of cognitive delay, however, underlying mechanisms are unknown. We employed morphological, transcriptomic and physiological methods to extensively characterize microglia in the immature hippocampus following S. epidermidis infection. 3D morphological analysis revealed activation of microglia after S. epidermidis. Differential expression combined with network analysis identified NOD-receptor signaling and trans-endothelial leukocyte trafficking as major mechanisms in microglia. In support, active caspase-1 was increased in the hippocampus and using the LysM-eGFP knock-in transgenic mouse, we demonstrate infiltration of leukocytes to the brain together with disruption of the blood–brain barrier. Our findings identify activation of microglia inflammasome as a major mechanism underlying neuroinflammation following infection. The results demonstrate that neonatal S. epidermidis infection share analogies with S. aureus and neurological diseases, suggesting a previously unrecognized important role in neurodevelopmental disorders in preterm born children.

Original languageEnglish
JournalGlia
Volume71
Issue9
Pages (from-to)2234-2249
Number of pages16
ISSN0894-1491
DOIs
Publication statusPublished - Sept 2023

Keywords

  • blood–brain barrier
  • hippocampus
  • leukocytes infiltration
  • microglia
  • perinatal brain
  • perinatal infection
  • Staphylococcus epidermidis
  • transcriptome analysis
  • WGCNA

Fingerprint

Dive into the research topics of 'Transcriptome network analysis links perinatal Staphylococcus epidermidis infection to microglia reprogramming in the immature hippocampus'. Together they form a unique fingerprint.

Cite this