Central nervous system (CNS) invasion by bacteria leads to severe infection, which can be fatal or associated with severe sequelae.1,2
Among the bacteria that can access the CNS, Listeria monocytogenes
), a Gram-positive facultative intracellular bacterium, has the ability to induce meningitis and encephalitis.
The first known isolate of Lm
was obtained from the cerebrospinal fluid (CSF) of a soldier who died from meningitis in 1918. The report was published in 1921,3
before the characterization of a new bacterial species in 1926 from infected laboratory rabbits and guinea pigs4
and in 1927 from wild gerbils.5
This species is now known as Listeria monocytogenes
. However, it is only during the second half of the 20th century that listeriosis started to be considered as a prominent human infection, concomitant with changes in food habits and the introduction of immunosuppressive therapies, in addition to being a well-characterized zoonosis routinely observed in domestic ruminants. The first human listeriosis outbreak linked to the absorption of contaminated food was published in 1983,6
is now regarded as a classic foodborne pathogen for veterinarians and clinicians, which is well known to infect ruminants and humans via the oral route, and target similar organs: the central nervous system and the fetoplacental unit.7
Even if listeriosis is rare in human (0.1 to 10 cases/million; 0.1% of all foodborne infections), it is considered as the most severe bacterial foodborne infection, responsible for 1,645 cases in Europe in 2009 (4 cases/million) for a case fatality rate of 16.6%8
and around 2,500 cases per year in the USA, associated with a lethality of up to 30% in case of neurological involvement, even when appropriately treated.9,10
More than 50% of the cases correspond to septicemia, around 20–25% to CNS infections, 10–15% to maternal-fetal infections and the remaining to various localized infections (compiled data from the French National surveillance system in the past 5 years). After a decrease in the number of cases in the second part of the 20th century, which correlates with the implementation of controls in food industry and information campaigns directed to pregnant women,11,12
the incidence of Lm
has slightly re-increased in recent years, notably in Europe.8,13-16
The reason for this increase is unknown, but is likely a combination of the relative increase of the population at risk for listeriosis, such as the immunosuppressed host and/or elderly, and changes in food processing and habits.
The intracellular life of Lm
and immune responses to this bacterium have been extensively studied in vitro and in vivo,17,18
yet many aspects of the pathophysiology of listeriosis, and particularly that of neurolisteriosis remain elusive, in part due to a relative lack of relevant and easy-to-handle animal model that reproduces all the hallmarks of the human disease (see below). Despite these limitations, epidemiological and clinical studies in human and ruminant as well as in vitro and in vivo mouse experimental infections, allow making a general picture of the putative mechanisms of Lm
CNS invasion and infection. These studies suggest that diverse pathways could be used by Lm
to gain access to the CNS and could include a retrograde neural route of invasion and crossing of the blood-brain barrier (BBB) by blood-borne bacteria.19,20
Yet, the molecular factors on both bacterial and host sides remain to be discovered, and new animal models recently developed will likely be instrumental to study and better understand the molecular mechanisms underlying neurolisteriosis (see below).