Immunopathogenesis of Craniotomy Infection and Niche-Specific Immune Responses to Biofilm

Abstract

Bacterial infections in the central nervous system (CNS) can be life threatening and often impair neurological function. Biofilm infection is a complication following craniotomy, a neurosurgical procedure that involves the removal and replacement of a skull fragment (bone flap) to access the brain for surgical intervention. The incidence of infection following craniotomy ranges from 1% to 3% with approximately half caused by Staphylococcus aureus (S. aureus). These infections present a significant therapeutic challenge due to the antibiotic tolerance of biofilm and unique immune properties of the CNS. Previous studies have revealed a critical role for innate immune responses during S. aureus craniotomy infection. Experiments using knockout mouse models have highlighted the importance of the pattern recognition receptor Toll-like receptor 2 (TLR2) and its adaptor protein MyD88 for preventing S. aureus outgrowth during craniotomy biofilm infection. However, neither molecule affected bacterial burden in a mouse model of S. aureus brain abscess highlighting the distinctions between immune regulation of biofilm vs. planktonic infection in the CNS. Furthermore, the immune responses elicited during S. aureus craniotomy infection are distinct from biofilm infection in the periphery, emphasizing the critical role for niche-specific factors in dictating S. aureus biofilm-leukocyte crosstalk. In this review, we discuss the current knowledge concerning innate immunity to S. aureus craniotomy biofilm infection, compare this to S. aureus biofilm infection in the periphery, and discuss the importance of anatomical location in dictating how biofilm influences inflammatory responses and its impact on bacterial clearance.

Exploring epigenetic reprogramming during central nervous system infection

“…The distinct origin of microglia as well as the unique microenvironment of the CNS necessitates specific investigation of microglial epigenetic activity separate from bone marrow‐derived macrophages. While CNS‐infiltrating macrophages and microglia exhibit some overlap in gene expression upon activation, 36 discrete surface marker expression and transcriptional differences allow for discrimination between the cell types 35 . Functionally, microglia can exert either pro‐ or anti‐inflammatory roles in the brain corresponding to polarization along an inflammatory spectrum 37 .…”

“…Monocytes are bone marrow‐derived mononuclear phagocytes which differentiate into macrophages upon migration into peripheral tissues 35 . The CNS harbors several resident macrophage populations, including perivascular, meningeal, and choroid plexus macrophages.…”

“…34 Although they share many attributes with macrophages, microglia possess unique capabilities and serve specialized functions within the CNS. 34 Microglia comprise around 10% of the cells in the brain parenchyma 35 and proliferate slowly under steady-state conditions, or rapidly in response to inflammatory stimuli (infection, proinflammatory cytokines, tissue damage, etc) 33 to repopulate the compartment with no contribution from bone marrow-derived monocytes. 34 The distinct origin of microglia as well as the unique microenvironment of the CNS necessitates specific investigation of microglial epigenetic activity separate from bone marrow-derived macrophages.…”

Metabolomic Characterization of Cerebrospinal Fluid from Intracranial Bacterial Infection Pediatric Patients: A Pilot Study

“…Pathogens, however, can still invade the CNS from blood, surrounding tissues or nerves [14]. Intracranial surgery, on the other hand, can severely disrupt the physiological and immunological barriers in the CNS, leaving the CNS susceptible to various pathogens [15]. Nowadays, intracranial bacterial infection remains a major cause of morbidity and mortality in neurosurgical cases [16].…”

The Prospect of Nanoparticle Systems for Modulating Immune Cell Polarization During Central Nervous System Infection

“…Many of the pathogens that invade the CNS are opportunistic and exploit patients with primary immune deficiencies that worsen disease severity (6,7). Other CNS infections can arise from complications following neurosurgical procedures, such as craniotomy and cerebrospinal fluid (CSF) shunt placement (8)(9)(10). The expanded use of therapeutics targeting immune effector mechanisms, such as monoclonal antibodies to inhibit cytokine action or leukocyte trafficking, can increase susceptibility to CNS infection (11)(12)(13).…”