Transcriptional Diversity and Niche-Specific Distribution of Leukocyte Populations during Staphylococcus aureus Craniotomy-Associated Biofilm Infection.
Amy L AldrichChristopher M HornCortney E HeimLee E KorshojTammy KielianPublished in: Journal of immunology (Baltimore, Md. : 1950) (2021)
Neurosurgery for brain tumor resection or epilepsy treatment requires a craniotomy to gain access to the brain. Despite prophylactic measures, infectious complications occur at a frequency of 1-3%, with approximately half caused by Staphylococcus aureus (S. aureus) that forms a biofilm on the bone flap and is recalcitrant to antibiotics. Using single-cell RNA sequencing in a mouse model of S. aureus craniotomy infection, this study revealed the complex transcriptional heterogeneity of resident microglia and infiltrating monocytes in the brain, in addition to transcriptionally diverse granulocyte subsets in the s.c. galea and bone flap. In the brain, trajectory analysis identified the transition of microglia from a homeostatic/anti-inflammatory to proinflammatory and proliferative populations, whereas granulocytes in the brain demonstrated a trajectory from a granulocyte myeloid-derived suppressor cell (MDSC)-like phenotype to a small population of mature polymorphonuclear neutrophils (PMNs). In the galea, trajectory analysis identified the progression from two distinct granulocyte-MDSC-like populations to PMN clusters enriched for IFN signaling and cell cycle genes. Based on their abundance in the galea and bone flap, PMNs and MDSCs were depleted using anti-Ly6G, which resulted in increased bacterial burden. This revealed a critical role for PMNs in S. aureus containment because MDSCs were found to attenuate PMN antibacterial activity, which may explain, in part, why craniotomy infection persists in the presence of PMN infiltrates. These results demonstrate the existence of a transcriptionally diverse leukocyte response that likely influences the chronicity of S. aureus craniotomy infection.
Keyphrases
- single cell
- staphylococcus aureus
- peripheral blood
- rna seq
- cell cycle
- soft tissue
- resting state
- white matter
- mouse model
- bone mineral density
- pseudomonas aeruginosa
- functional connectivity
- biofilm formation
- high throughput
- inflammatory response
- gene expression
- cell proliferation
- anti inflammatory
- transcription factor
- bone loss
- patient safety
- bone regeneration
- genome wide
- risk factors
- stem cells
- cystic fibrosis
- escherichia coli
- oxidative stress
- microbial community
- spinal cord injury
- postmenopausal women
- breast reconstruction
- multiple sclerosis
- heat shock
- bone marrow
- recombinant human
- mesenchymal stem cells
- wastewater treatment
- subarachnoid hemorrhage
- heat shock protein
- antibiotic resistance genes