Transcriptome network analysis links perinatal Staphylococcus epidermidis infection to microglia reprogramming in the immature hippocampus.
Giacomo GravinaMaryam ArdalanTetyana ChumakHalfdan RydbeckXiaoyang WangCarl Joakim EkCarina MallardPublished in: Glia (2023)
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.
Keyphrases
- biofilm formation
- network analysis
- inflammatory response
- candida albicans
- staphylococcus aureus
- pseudomonas aeruginosa
- preterm infants
- neuropathic pain
- cerebral ischemia
- low birth weight
- escherichia coli
- single cell
- cognitive impairment
- lipopolysaccharide induced
- pregnant women
- endothelial cells
- rna seq
- white matter
- lps induced
- multidrug resistant
- gene expression
- peripheral blood
- brain injury
- spinal cord injury
- young adults
- oxidative stress
- preterm birth
- subarachnoid hemorrhage
- prefrontal cortex
- drug resistant
- gestational age
- acinetobacter baumannii
- spinal cord
- multiple sclerosis
- klebsiella pneumoniae
- methicillin resistant staphylococcus aureus