Listeria monocytogenes is a gram positive facultatively intracellular foodborne pathogen, which is often found in food and elsewhere in nature. Listeria can survive temperatures from below freezing to body temperature (Ramaswamy et al., 2007). Infection by L. monocytogenes causes the disease listeriosis. The manifestations of listeriosis include septicemia, meningitis (or meningoencephalitis), encephalitis, corneal ulcer, pneumonia, and intrauterine or cervical infections in pregnant women, which may result in spontaneous abortion (2nd/3rd trimester) or stillbirth (Wiki: L. monocytogenes).
4. Microbial Pathogenesis
L. monocytogenes may invade the gastrointestinal epithelium. Once the bacterium enters the host's monocytes, macrophages, or polymorphonuclear leukocytes, it becomes blood-borne (septicemic) and can grow. Its presence intracellularly in phagocytic cells also permits access to the brain and probably transplacental migration to the fetus in pregnant women. The pathogenesis of L. monocytogenes centers on its ability to survive and multiply in phagocytic host cells (Wiki: L. monocytogenes). Listeria is able to move from cell to cell via actin motility (Ramaswamy et al., 2007).
5. Host Ranges and Animal Models
Listeria can live in the intestines of humans, animals and birds without causing symptoms. Mice are used as a model of infection for listeria (Ramaswamy et al., 2007).
6. Host Protective Immunity
Infection is often controlled by cell mediated response. Infection is asymptomatic in most patients, and tends to be more severe in immunocompromised individuals (Ramaswamy et al., 2007).
Molecule Role Annotation :
An actA mutant is attenuated in mice and induced significant protection from challenge with wild type L. monocytogenes (Darji et al., 2003).
Molecule Role Annotation :
In an attempt to generate a subunit vaccine in this experimental disease model, eukaryotic plasmid DNA expression vectors containing genes encoding either the wild-type or modified forms of recombinant listeriolysin O (hly) were generated and used for genetic vaccination of naive mice. Results of these studies indicate that the intramuscular immunization of mice with specifically designed plasmid DNA constructs encoding recombinant forms of listeriolysin O (hly) stimulates peptide-specific CD8+ immune T cells that exhibit in vitro cytotoxic activity. More importantly, such immunization can provide protective immunity against a subsequent challenge with viable L. monocytogenes (Cornell et al., 1999).
Molecule Role Annotation :
Mice immunized with p60 encapsulated in liposomes launched a strong CTL response and were protected against a subsequent challenge with L. monocytogenes (Grenningloh et al., 2008).
Molecule Role Annotation :
A plcB mutant, in combination with an actA mutant, is attenuated in mice and induces significant protection from challenge with wild type L. monocytogenes (Darji et al., 2003).
Molecule Role Annotation :
IFN-gamma plays a critical role in Th1 type immune response. It is important for protection against infections by various viruses and intracellular bacteria.
Additional Molecule Role :
Vaximmutor
Additional Molecule Role Annotation :
The experimental data demonstrated that three time vaccinations with BCG in BALB/c mice induced strong TB Ag-specific IFN-gamma immune responses in splenocytes (Wang et al., 2009).
Vaccination Protocol:
For immunization with the plasmid constructs, 6-to 8-wk-old mice received the first of a series of three i.m. immunizations (via the tibialis anterior muscles) at 3- to 4-wk intervals with ~100–125 µg of plasmid DNA in 50 µl of normal saline. Normal control mice received either no immunization or were immunized with either 0.2 ml of PBS (i.v.) or 50 µl of saline (i.m.) (Cornell et al., 1999).
Challenge Protocol:
Briefly, groups of normal or immunized BALB/c mice received an i.v. injection with ~2 LD50 (~20,000 CFU) of L. monocytogenes in 0.2 ml of PBS, at 3–4 wk following the final immunization with plasmid DNA. Control groups consisted of normal (nonimmunized) mice and mice previously immunized (4–12 wk earlier) with a sublethal injection of viable L. monocytogenes (Cornell et al., 1999).
Efficacy:
DNA immunization of mice provides protection against challenge with viable L. monocytogenes (Cornell et al., 1999).
Vaccination Protocol:
BALB/c mice (two mice/group) were immunized i.p. with 100 μl liposomes containing approximately 3 μg of p60 antigen shown (Grenningloh et al., 2008).
Challenge Protocol:
BALB/c mice were immunized with encapsulated p60 and challenged intravenously on day 9 after immunization with 5 × 10^3 (1 × LD50) L. monocytogenes (Grenningloh et al., 2008).
Efficacy:
Mice immunized with p60 encapsulated in liposomes launched a strong CTL response and were protected against a subsequent challenge with L. monocytogenes (Grenningloh et al., 2008).
Persistence:
An actA/plcB mutant is attenuated in mice (Darji et al., 2003).
Efficacy:
An actA/plcB mutant induces significant protection in mice from challenge with wild type L. monocytogenes (Darji et al., 2003).
Host Gene Response of
Ifng (Interferon gamma)
Gene Response:
The ΔactAΔplcB mutant is able to induce sufficient IFN-γ in mice to prevent a Th1 to Th2 switch and retains its ability to induce a strong CD8+-mediated T cell response, even though the amount of IFN-gamma produced is less than that produced after infection with the wild type strain (Darji et al., 2003).
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