Evidence for Intraaxonal Spread of Listeria Monocytogenes from the Periphery to the Central Nervous System

Abstract

Rhombencephalitis due to Listeria monocytogenes is characterized by progressive cranial nerve palsies and subacute inflammation in the brain stem. In this paper, we report observations made on mice infected with L. monocytogenes. Unilateral inoculation of bacteria into facial muscle, or peripheral parts of a cranial nerve, induced clinical and histological signs of mainly ipsilateral rhombencephalitis. Similarly, unilateral inoculation of bacteria into lower leg muscle or peripheral parts of sciatic nerve was followed by lumbar myelitis. In these animals, intraaxonal bacteria were seen in the sciatic nerve and its corresponding nerve roots ipsilateral to the bacterial application site. Development of myelitis was prevented by transsection of the sciatic nerve proximally to the hindleg inoculation site. Altogether, our results support the hypothesis that Listeria rhombencephalitis is caused by intraaxonal bacterial spread from peripheral sites to the central nervous system.

Listeria monocytogenes Spreads within the Brain by Actin-Based Intra-Axonal Migration

“…The efficient spread of L. monocytogenes could be explained by its ability to move from cell to cell, which permits the agent to multiply and diffuse within tissues protected from the host defenses by avoiding contact with the extracellular compartment (19). In view of the observed ability of L. monocytogenes to spread within cranial nerves (25,26), our previous studies showing progression of the lesions within the brain (17) and the sporadic association of L. monocytogenes with axons in the hippocampal slice model (30), we hypothesized that intercellular spread of the agent in the CNS could also be intra-axonal. Moving within axons, a highly interconnected network with little or no major histocompatibility complex (MHC) expression (29,31), would, at least temporarily, allow L. monocytogenes to escape immune detection while efficiently spreading to distant CNS regions.…”

“…In rhombencephalitis, which frequently occurs in otherwise healthy human patients and ruminants (1,9,11,(21)(22)(23), there is strong evidence for the entry of the bacteria into the brainstem by the axonal migration of L. monocytogenes along various cranial nerves (17,18,24,25). This includes localization of L. monocytogenes in cranial nerve axons (24)(25)(26)(27), frequent involvement of cranial nerve nuclei (17,18), isolation of L. monocytogenes from the brain but not from other organs (28), and demonstration of E-cadherin, a major receptor for L. monocytogenes entry, in cranial nerves of ruminants (27).…”

Listerial brainstem encephalitis – treatable, but easily missed

“…[9] Injection of listerial bacteria into the facial nerves of mice was followed 5 10 days later by ipsilateral CNS deficits that were prevented by section of the nerve proximal to the inoculation site. [10] Similarly, injection of listerial bacteria into the sciatic nerves of mice resulted in a flaccid paraparesis that was prevented by sectioning the sciatic nerve proximal to the inoculation site. [10] Actin dependent locomotion of L. monocytogenes along microtubules has been demonstrated in other eukaryote cells and remains the most plausible explanation for bacterial propagation along axons.…”

“…[10] Similarly, injection of listerial bacteria into the sciatic nerves of mice resulted in a flaccid paraparesis that was prevented by sectioning the sciatic nerve proximal to the inoculation site. [10] Actin dependent locomotion of L. monocytogenes along microtubules has been demonstrated in other eukaryote cells and remains the most plausible explanation for bacterial propagation along axons. [11] Factors predisposing to LBE in humans have not been identified.…”

Neurolisteriosis en adultos: a propósito de seis casos clínicos

“…El agente penetraría al organismo por vía digestiva, desde donde se disemina, produciendo de p re f e rencia, cuadros bacteriémicos y neuro l ó g ic o s 1 , 5 . Por experimentación animal se plantea la hipótesis de que la romboencefalitis porL i s t e r i a estaría causada por difusión bacteriana intraaxonal desde sitios periféricos del sistema nervioso 9 . Aunque L. monocytogenes tiene especial pre d ilección por el Sistema Nervioso central (SNC) y la placenta, como resultado de la difusión sanguínea puede observarse infección en otras localizaciones: a rtritis séptica, endocarditis, osteomielitis, peritonitis, empiema pleural, abscesos hepáticos, endoftalmitis, etc 1 , 3 , 5 , 6 , 7 , 1 0 .…”