Transcriptome network analysis links perinatal Staphylococcus epidermidis infection to microglia reprogramming in the immature hippocampus - PubMed (original) (raw)

. 2023 Sep;71(9):2234-2249.

doi: 10.1002/glia.24389. Epub 2023 May 29.

Affiliations

Giacomo Gravina et al. Glia. 2023 Sep.

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.

Keywords: Staphylococcus epidermidis; WGCNA; blood-brain barrier; hippocampus; leukocytes infiltration; microglia; perinatal brain; perinatal infection; transcriptome analysis.

© 2023 The Authors. GLIA published by Wiley Periodicals LLC.

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References

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