Characterization of a Listeria monocytogenes meningitis mouse model

Abstract

BackgroundListeria monocytogenes is a common cause of bacterial meningitis. We developed an animal model of listerial meningitis.MethodsIn survival studies, C57BL/6 mice received intracisternal injections with different L. monocytogenes sequence type 1 (ST1) colony forming units per milliliter (CFU; n = 48, 105, 106, 107, 108, and 109 CFU/ml). Second, mice were inoculated with 108 CFU/ml ST1 and sacrificed at 6 h and 24 h (n = 12/group). Outcome parameters were clinical score, CFUs, cyto- and chemokine levels, and brain histopathology. Third, 84 mice were inoculated (109 CFU/ml ST1) to determine optimal antibiotic treatment with different doses of amoxicillin and gentamicin. Fourth, mice were inoculated with 109 CFU/ml ST1, treated with amoxicillin, and sacrificed at 16 h and 24 h (n = 12/group) for outcome assessment. Finally, time point experiments were repeated with ST6 (n = 24/group).ResultsMedian survival time for inoculation with 108 and 109 CFU/ml ST1 was 46 h and 40 h; lower doses of bacteria led to minimal clinical signs of disease. Brain levels of IL-6, IL-17A, and IFN-γ were elevated at 24 h, and IL-1β, IL-6, IL-10, IFN-γ, and TNF-α were elevated in blood at 6 h and 24 h. Histopathology showed increased meningeal infiltration, vascular inflammation of meningeal vessels, hemorrhages, and ventriculitis. In the treatment model, brain levels of IL-6 and IL-17A and blood levels of IL-6 and IFN-γ were elevated. Compared to ST6, infection with ST1 led initially to higher levels of IL-1β and TNF-α in blood and more profound neuropathological damage. At 16 h post inoculation, IL-1β, IL-10, and TNF-α in blood and IL-6, IL17A, TNF-α, and IFN-γ levels in brain were higher in ST1 compared to ST6 without differences in CFUs between STs. At 24 h, neuropathology score was higher in ST1 compared to ST6 (p = 0.002) infected mice.ConclusionsWe developed and validated a murine model of listerial meningitis. ST1-infected mice had a more severe inflammatory response and brain damage as compared to ST6-infected mice.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1293-3) contains supplementary material, which is available to authorized users.

Retrospective Study of Listeria monocytogenes Isolated in the Territory of Inner Eurasia from 1947 to 1999

“…The predominant clonal complexes in China are CC9 and CC8 in food and ST87 in clinics [53,54]. In the last decade, CC6 noticeably increased in significance as a causative agent of human listeriosis in Africa, Europe, and North America [31,33,[55][56][57]. In Russia, current human listeriosis is associated with the CC1, CC2, and CC20 strains [38].…”

The TRAPs From Microglial Vesicles Protect Against Listeria Infection in the CNS

“…Meningitis was induced by transcutaneous intracisternal injection of 10 μl of a bacterial suspension containing 10 5 colony-forming units (CFU) of Listeria or PBS. Mice were monitored every 4–6 h (starting from 12 h after inoculation), and the clinical manifestations were observed including activity, respiration rate, breathing, food intake and neurological signs (Mook-Kanamori et al, 2012; Koopmans et al, 2018). Any animal that appeared moribund prior to the designated endpoint would be humanely euthanized, and death was recorded as occurring the next day.…”

Past and Current Perspectives in Modeling Bacteria and Blood–Brain Barrier Interactions

“…Typically, these models can be distinguished mainly by the route of injection. Direct infection of the CNS through intra-cerebral or intra-cisternal route allows for the monitoring of host–pathogen interactions once the pathogen is in the CNS as well as leukocyte transmigration (Shapiro et al, 2000; Koedel et al, 2001; Grandgirard et al, 2007; Reiß et al, 2011; Koopmans et al, 2018). While this method is useful, it lacks a more natural course of dissemination through the blood stream (Chiavolini et al, 2008).…”