The role of CNS macrophages in streptococcal meningoencephalitis

Abstract

In the healthy brain, microglia and other CNS macrophages are the most abundant immune cell type. Thus, they form the natural immune cell interface with streptococci, which are the leading cause of bacterial meningitis and encephalitis in infants and young children. In homeostasis, the blood-brain barrier allows for very limited access of immune cells circulating in the periphery. During bacterial meningoencephalitis, however, origin and fate of CNS macrophages are massively altered. This review summarizes the emerging knowledge on the sequence of reciprocal events between streptococci and CNS macrophages leading to host resistance, acute inflammation, changes in resident innate immune cells of the brain, and long-term neuronal damage. K E Y W O R D S meningitis, microglia, Streptococcus agalactiae, Streptococcus pneumoniae [The copyright line for this article was changed on 25 February 2019 after original online publication] of events can transiently severely perturb the separation of the CNS and the peripheral immune system. Thereby, long-term consequences for neurodevelopment might ensue.

CNS Macrophages and Infant Infections

“…This is in line with the observation that over 30% of children that survived GBS meningitis suffer from neurodevelopmental impairment (128). As previously suggested, the exact role of microglia and CAMs in GBS mediated meningoencephalitis remains ill-defined and needs to be further explored (337).…”

“…Infection with GBS is particularly dangerous for newborns presenting a high rate of morbidity of infected individuals who survive the primary neonatal infection ( 334 ). GBS is a major, potentially lethal cause of bacterial meningitis in newborns which is an infection of the CNS membranes covering brain and spinal cord ( Table 1 ) ( 335 – 337 ). Affected newborns most frequently suffer from neurological consequences such as cerebral palsy, cognitive retardation, loss of vision and hearing and seizures ( Table 1 ) ( 127 ).…”

“…Late onset sepsis often leads to meningoencephalitis which has a mortality rate currently of around 8.3% ( Table 1 ) ( 340 ). Here, an intestinal route of GBS infection was suggested in neonates ( 337 ). Often GBS enter via the microvasculature in the choroid plexus where they adhere to endothelial cells and are able to cross the BBB either paracellularly, via transcytosis or exploiting trafficking phagocytic host cells ( 342 , 343 ).…”

“…Often GBS enter via the microvasculature in the choroid plexus where they adhere to endothelial cells and are able to cross the BBB either paracellularly, via transcytosis or exploiting trafficking phagocytic host cells ( 342 , 343 ). In the interfaces of the brain, they encounter, besides recruited circulating monocytes, also the resident perivascular and meningeal macrophages ( 337 ). It was shown that perivascular and meningeal macrophages play an important role during bacterial infection of the CNS by secreting pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 and phagocytose invading bacteria ( Figure 3 ) ( 344 ).…”

Cytomegaloviruses and Macrophages—Friends and Foes From Early on?

“…Thereby, monocyte-derived MACs might represent a potential way of viral dissemination from CNS interfaces into the brain parenchyma (186,190). Accordingly, infection of MACs in the CNS may lead to heavy reorganization of otherwise tightly regulated immune cell populations, which may contribute to different pathologies (191)(192)(193).…”