Molecular and cellular mechanisms for microbial entry into the CNS

Abstract

A number of pathogenic microbes including neuroinvasive viruses, bacteria and parasites are capable of entry into the central nervous system (CNS) and cause a variety of clinical manifestations. The cellular and molecular mechanisms for the CNS invasion have been extensively studied in the last two decades. Viruses invade neurons and thereby cause encephalitis or peripheral neuritis, while bacteria enter the cerebrospinal¯uid (CSF) and cause meningitis. In contrast, the mechanisms for parasitic neuroinvasion are much more complex and less clear. The capabilities that enable these elite subsets of pathogens to engineer uptake into the CNS will be the subject of this review.

Recombinant Semliki Forest virus vaccine vectors: the route of injection determines the localization of vector RNA and subsequent T cell response

“…Entry of the non-spreading virus could in the present study have occurred either by passage across cerebral EC, 21 or via olfatory and trigemial nerves 22 or through migration of virally infected leukocytes. 23 An argument against at least the latter explanation is that blood was found negative for vector transcripts. A more likely explanation could be that the PCR signal from the brain material reflects infection of cells directly accessible from the circulation such as ECs.…”

Experimental Pneumococcal Meningitis in Mice: A Model of Intranasal Infection

“…Subsequently, the suspension was washed twice in sterile isotonic saline and was resuspended in sterile isotonic saline, which corresponded to cfu/mL. The 8 3 ϫ 10 exact number of colony-forming units was determined retrospectively by the growth of serial dilutions on blood agar plates. Synthetic hyaluronidase (0, 180, 360, or 560 U; Sigma) was added to the inoculum.…”

“…In this study, we sought to establish a mouse model of pneumococcal meningitis that mimics the common route of infection in human disease (i.e., colonization of the upper respiratory tract mucosa, which is followed by invasion of bacteria into the bloodstream and subsequent invasion of the central nervous system [CNS] via the blood-brain barrier [BBB]) [8,9]. For that reason, we added increasing doses of purified hyaluronidase to intranasally inoculated S. pneumoniae.…”

Virus-Induced Encephalitis and Innate Immune Responses – A Focus on Emerging or Re-Emerging Viruses

“…Third, viruses can also penetrate the CNS by taking advantage of incomplete closure of the BBB. Despite the intercellular tight junctions between the capillary endothelial cells in most regions of the BBB, certain areas of the CNS such as the choroid plexus, posterior pituitary, and circumventricular organs are not completely protected by the BBB due to a fenestrated endothelial cell layer and sparse basement membrane (Zhang and Tuomanen, 1999). A number of blood-borne viruses including mumps (Herndon et al, 1974), HIV (Bagasra et al, 1996) and CHIKV (Couderc et al, 2008) have been suggested to penetrate across the choroid plexus micro-vessels and infect the epithelium.…”