Animal models of listeriosis: a comparative review of the current state of the art and lessons learned

Abstract

Listeriosis is a leading cause of hospitalization and death due to foodborne illness in the industrialized world. Animal models have played fundamental roles in elucidating the pathophysiology and immunology of listeriosis, and will almost certainly continue to be integral components of the research on listeriosis. Data derived from animal studies helped for example characterize the importance of cell-mediated immunity in controlling infection, allowed evaluation of chemotherapeutic treatments for listeriosis, and contributed to quantitative assessments of the public health risk associated with L. monocytogenes contaminated food commodities. Nonetheless, a number of pivotal questions remain unresolved, including dose-response relationships, which represent essential components of risk assessments. Newly emerging data about species-specific differences have recently raised concern about the validity of most traditional animal models of listeriosis. However, considerable uncertainty about the best choice of animal model remains. Here we review the available data on traditional and potential new animal models to summarize currently recognized strengths and limitations of each model. This knowledge is instrumental for devising future studies and for interpreting current data. We deliberately chose a historical, comparative and cross-disciplinary approach, striving to reveal clues that may help predict the ultimate value of each animal model in spite of incomplete data.

Dose Response of Listeria monocytogenes Invasion, Fetal Morbidity, and Fetal Mortality after Oral Challenge in Pregnant and Nonpregnant Mongolian Gerbils

“…Additionally, only 50% of litters from 10 7 -CFU-treated gerbils were invaded, none of which showed L. monocytogenes-induced resorptions or stillbirths, whereas guinea pigs had fetal invasion in dams exposed to 10 5 CFU and stillbirths in all groups exposed to Ն10 6 CFU. These results can be further contrasted with those for nonhuman primates, a model that is also permissive to both InlA and InlB invasion pathways (15), where stillbirths occurred in animals exposed to as little as 10 3 CFU (25); if invasion in gerbils is indeed similar to invasion in primates and humans, we would have expected more stillbirths to occur at lower doses than 10 9 CFU in gerbils. Taken together, these results indicate that permissiveness to InlA-and InlB-dependent invasion pathways is insufficient to explain the susceptibility of various animals to L. monocytogenes, and they offer further evidence that other mechanisms or pathways may contribute to susceptibility in humans.…”

“…Various animals have been used as models, but some of the most common are lacking in one or both of these areas. Listeriosis in nonhuman primates is perhaps most similar to listeriosis in humans (15). However, it can be difficult to acquire large numbers of primates for a single study.…”

How the Study of Listeria Monocytogenes has Led to New Concepts in Biology

“…A variety of other species such as gerbils, guinea pigs, zebrafishes, wax moths, chicken embryos, non-human primates have also occasionally been used (for reviews, [9,122,123]). However, it is extremely difficult to have an optimal animal model that mimics perfectly the infection process in humans, especially knowing that listeriosis appears to be an infection of immuno-compromised individuals.…”

Editorial

“…Intra-axonal bacterial migration and possibly also the innate immune response play an important role in the intracerebral spread of the agent and hence the progression of listeric rhombencephalitis in ruminants (Henke et al 2015). It should be realized that much has been learned about L. monocytogenes since its first isolation from naturally infected rodents, but truly suitable animal models of infection are so far still missing, and many uncertainties remain when animal models are employed to model human infection (Hoelzer et al 2012).…”

“…Sheep appears to be particularly susceptible to infection, but listeriosis is also common in a variety of other polygastric species, and L. monocytogenes has, for instance, been isolated from cattle, goats, llamas, alpacas, deer, reindeer, antelopes, water buffalos and moose. It is worth mentioning that bacterial shedding in the absence of clinical symptoms has occasionally been observed (Hoelzer et al 2012).…”