Targeting of the central nervous system byListeria monocytogenes

Abstract

Among bacteria that reach the central nervous system (CNS), Listeria monocytogenes (Lm) is one of deadliest, in human and ruminant. This facultative intracellular bacterium has the particularity to induce meningitis, meningoencephalitis and rhombencephalitis. Mechanisms by which Lm accesses the CNS remain poorly understood, but two major routes of infection have been proposed, based on clinical, in vitro and in vivo observations. A retrograde neural route is likely to occur in ruminants upon crossing of the oral epithelium, and this probably accounts for the observation that Lm induces almost exclusively rhombencephalitis in these animals. In contrast, the hematogenous route is likely the most frequent in human, in whom bacteria circulating in the blood, either free or associated with leukocytes are thought to breach the blood-brain barrier. New animal models that faithfully reproduce the hallmarks of human neurolisterisosis will allow addressing the molecular mechanisms underlying Lm ability to induce CNS disease, and improve our understanding of the pathophysiology of this deadly infection.

Listeria monocytogenes infection in ruminants: Is there a link to the environment, food and human health? A review

“…However, subsequent mechanisms to access the brain are likely to differ between host species. In humans, it is assumed that L. monocytogenes passes the gastrointestinal barrier and spreads haematogenously to the brain (Nikitas et al, 2011;Disson and Lecuit, 2012). In ruminants, there are indications that the pathogen enters the cranial nerves via the oral epithelium or conjunctivae (Charlton and Garcia, 1977).…”

Listerial brainstem encephalitis – treatable, but easily missed

“…With CNS invasion, listeriosis may target the meninges resulting in the typical clinical picture of acute/subacute bacterial meningitis, [2] but unlike other bacteria may also target the brain parenchyma and specifically the rhombencephalon (pons, medulla, cerebellum). In humans, brainstem infection occurs in up to 11 24% of patients with CNS listeriosis.…”

“…This presentation is probably accounted for by a novel route of infection that exploits retrograde axonal transport to the brainstem along the cranial nerves that supply the oropharynx. [2,6] …”

“…The organism has a remarkable resistance to eradication during food processing, has unique virulence factors, [1,2] and is an important cause of foodborne epidemic disease with high associated mortality. [3] Following ingestion, infection occurs across the intestinal epithelium and spreads to the liver, where it becomes established within the cytosol of macrophages.…”

“…Listerial meningitis may be the third most common cause of acute communityacquired bacterial meningitis. [2] Listerial brainstem meningitis (LBE), however, is an uncommon, sporadically occurring form of listerial infection that progresses rapidly and is invariably fatal unless treated early. [35] Cases are often undetected.…”