Where is listeria found in the body

People who are more likely to get a Listeria infection pregnant women , people 65 years or older , and people with a weakened immune system and those who prepare food for them can:.

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What are the symptoms of listeriosis? Pregnant women : Pregnant women typically experience only fever and other flu-like symptoms, such as fatigue and muscle aches. However, infections during pregnancy can lead to miscarriage, stillbirth, premature delivery, or life-threatening infection of the newborn. People other than pregnant women : Symptoms can include headache, stiff neck, confusion, loss of balance, and convulsions in addition to fever and muscle aches.

How is listeriosis diagnosed and treated? Listeriosis is treated with antibiotics. How do people get infected with Listeria? What should I do if I ate a food that may have been contaminated with Listeria?

Is listeriosis a serious disease? How many people get listeriosis every year? While a mother with a Listeria infection may not show any outward symptoms, an unborn child might be severely affected. Listeriosis can result in miscarriage or premature birth. There is a possibility that a newborn might suffer a life-threatening infection in the days and weeks after birth.

Listeriosis is caused by Listeria , a type of bacteria that is commonly found in water, soil, and feces. Humans are infected when they consume foods that harbor the bacteria. The most common foods to cause listeriosis outbreaks are deli meats and unpasteurized dairy products. However, many other foods have also been found to spark outbreaks, including caramel apples, cantaloupe, and cabbages fertilized by sheep manure. Adults who are healthy and have strong immune systems are less at risk of listeriosis.

The following are associated with an increased risk of Listeria infection:. For minor infections, medication might not be required. For more serious cases of listeriosis, antibiotics are the most common treatment choice; ampicillin can be used alone or in conjunction with another antibiotic often gentamicin. If septicemia or meningitis occur, the individual will be given intravenous antibiotics and require up to 6 weeks of care and treatment. Although listeriosis is rare, there are a number of ways to further reduce the chances of becoming infected; these precautions are especially important during pregnancy:.

Listeria has been found in at least 42 species of wild and domesticated animals, and 17 species of birds. The bacterium has been isolated from oysters, fish, crustaceans, ticks, and flies. Some studies suggest that up to 10 percent of human gastrointestinal tracts contain L. In short, Listeria is a successful organism. Its hardy characteristics, combined with its relative ubiquity make Listeria a serious, ongoing concern. However, in immunocompromised or other at-risk individuals, the infection may continue and eventually move to the brain.

The Listeria bacterium is able to enter and survive within immune cells such as macrophages. Within the cell, the bacteria can multiply and spread to neighboring cells, safe from the immune system. This Minireview will summarize recent epidemiologic and clinical information regarding L. Listeria monocytogenes is a Gram-positive, facultative intracellular bacterium that causes invasive diseases in humans and animals, especially central nervous system CNS infections Vazquez-Boland et al.

Although it is not the most common cause of CNS infection, L. In fact, an epidemiologic study of bacterial meningitis in the United States US in found that this bacterium is nearly fold more efficient than other neuroinvasive Gram-positive bacteria including Streptococcus pneumoniae and group B streptococci at invading the CNS once an invasive infection has been established Schuchat et al.

Listeria monocytogenes has been extensively studied as a model pathogen largely from the perspective of innate and adaptive immune responses to intracellular infection and bacterial entry and survival within mammalian cells Cossart, There is also a growing body of data concerning CNS infections caused by L.

This minireview begins with a brief overview of epidemiological data and the clinical manifestations of listeriosis then concentrates more specifically on the mechanisms by which L. Listeria monocytogenes is an uncommon human pathogen. It is mostly identified through cases of invasive disease, either associated with outbreaks or as sporadic infections, and through food safety programs. Nonperinatal cases of invasive listeriosis have an estimated worldwide incidence ranging from 0.

Listeria monocytogenes usually ranks as the third or fourth most common cause of bacterial meningitis in North America and Western Europe Durand et al. In calendar year , the most recent year for which complete statistics are available, cases of invasive listeriosis were reported to the US Centers for Disease Control and Prevention for an annual incidence of 0. In contrast, infection rates are much higher in populations considered to be at higher risk.

For example, the incidence during pregnancy has been estimated at c. Other at risk patients include those at extremes of age, those taking immunosuppressive medications following organ transplantation and those with immunocompromising illnesses including cancer, autoimmune diseases, alcoholism and diabetes mellitus Ciesielski et al.

Another interesting epidemiologic feature of L. Grif detected the organism in 3. Prolonged shedding was not detected and shedding did not correlate with overt illness. Further studies will be necessary to determine the impact of asymptomatic shedding on the acquisition of infection in others. The USDA issued food recalls in the 5 year period from to , The quantity of meat and poultry involved ranged from 5 lbs c. In these instances bacteria were isolated from a diverse array of products including dairy cheeses, raw milk , agricultural strawberries, cut fresh fruit, sliced mushrooms , and various ready to eat foodstuffs such as coleslaw, crab dip, smoked salmon and turkey, egg salad, potato salad, and macaroni salad.

Less common focal infections derived from hematogenous spread include endocarditis, peritonitis, septic arthritis or endopthalmitis Doganay, Focal infections including cholecystitis, prosthetic joint infection and infections of arterial grafts have also been described Alleberger et al. The role of L. Following an incubation period of 6—49 h median 20—25 h , most patients present with diarrhea, fever, abdominal pain, chills, headache and myalgias Dalton et al.

This is a self-limited disease with median durations of fever and diarrhea of 27 and 42 h, respectively, and most patients recover without antimicrobial treatment Dalton et al. Most women present with a bacteremic illness consisting of fever, chills, headache and leukocytosis with a 6—7 day illness before diagnosis McLauchlin, b ; Mylonakis et al.

The organism may be recovered from cultures of the cervix, amniotic fluid and placenta. Complications may include spontaneous abortion or stillbirth in c. Up to two-thirds of surviving neonates born to mothers with listeriosis develop overt neonatal infection due to transplacental transmission from maternal bacteremia, or from exposure during transit through a colonized vaginal canal.

Neonatal listeriosis is classified as either early occurring in the first 5—7 days following delivery or late infection Larsson et al. Early disease is often overt at time of delivery and associated with maternal infection. It presents as pneumonia, bacteremia, or meningitis. Meconium staining, respiratory distress, fever, lethargy, jaundice and rash are typically observed.

In some neonates, the infection manifests as granulomatosis infantiseptica in which there are widespread micro-abscesses and granulomata especially in the liver, spleen and lungs. In contrast, late onset infection usually occurs in full term neonates delivered from uncomplicated pregnancies.

It usually presents as meningitis with the presumed source of the organism from the mother's vaginal tract acquired at the time of delivery. Invasive L. The CSF protein is invariably elevated although hypoglycorrhachia is variably observed. Two less commonly observed CNS infections are brainstem encephalitis rhombencephalitis and brain abscess.

Rhombencephalitis accounts for c. The prodrome usually lasts 4—5 days then ends with the abrupt onset of neurological deficits; most commonly asymmetric cranial nerve palsies reflecting pontomedullary involvement. Many patients will also demonstrate cerebellar findings such as ataxia and dysmetria or long tract signs hemiparesis and hypesthesia. CSF Gram's stain rarely demonstrates the organism. CT scans may show hypodense lesions in the brainstem, but the superiority of MR imaging of the posterior fossa make it the radiological image of choice Soo et al.

Most survivors have significant neurological sequelae. Several investigators have described the clinical features of CNS abscesses caused by L.

Most patients are immunosuppressed or have comorbid diseases, especially those in which two or more brain abscesses are found Mylonakis et al.

The typical patient presents with fever, headache and focal neurological deficits. Meningismus is rarely observed. Blood cultures are usually positive while CSF cultures, when obtained, are positive in less than half Bartt, Lesions are best localized either by CT or MR imaging.

Isolates are generally susceptible to the clinically important antibiotics, however are usually resistant to the cephalosporins Heger et al. Ideally, an effective antibiotic must enter the host cells, bind to the penicillin-binding protein 3 PBP3 of Listeria and remain active in the unfavorable intracellular environment Hof et al. Based on animal studies, case reports and in vitro susceptibility testing, ampicillin and penicillin, often in combination with gentamicin, are the drugs of choice for these infections Hof et al.

Animal studies and in vitro data suggest a potential role for the newer fluoroquinolones, but clinical data are lacking Michelet et al. Care must be exercised with some antimicrobial combinations because they elicit antagonistic results in vitro. Despite the growing problems with antimicrobial resistance in gram-positive bacteria, antibiotic resistance is uncommon among human isolates of Listeria spp.

Poulsen et al. However, isolates are often intermediate or fully resistant to cephalothin, cefotaxime, cefepime, monobactams, d -ofloxacin and nalidixic acid Hof et al. Thus, cephalosporins are not recommended for the treatment of listerial infections.

Tetracycline resistance has been described Marco et al. An additional treatment consideration is the role of antibiotic tolerance.

Several laboratories have identified putative genetic loci that may regulate tolerance to bacteriocins, ampicillin and penicillin Stack et al. The case fatality rate of listeriosis is high reflecting both the underlying health status of patients and the virulence of the organism.

Other correlates of mortality include low Glasgow coma scale at admission, thrombocytopenia, elevated hepatic transaminases, inappropriate antibiotic treatment or use of vancomycin and extremes of age Skogberg et al. Listeria monocytogenes is unique among neuroinvasive bacteria in that in vitro and in vivo data suggest it has the potential to invade the CNS by at least three different mechanisms Drevets et al. These include 1 transport across the blood-brain or blood-choroid barriers within parasitized leukocytes, 2 direct invasion of endothelial cells by extracellular blood-borne bacteria, or 3 retrograde centripetal migration into the brain within the axons of cranial nerves.

Before considering neuroinvasive mechanisms, we will briefly review the microbiology of L. Readers are directed to recent reviews for in-depth discussions of this topics Hamon et al. Listeria monocytogenes can invade and replicate within a wide variety of mammalian cells. It can invade normally nonphagocytic cells such as endothelial cells, enterocytes, and fibroblasts, utilizing certain surface invasion proteins, of which internalin A InlA and internalin B InlB are the best studied Ireton, The cellular ligand for InlA is E-cadherin which is present at adherens junctions between epithelial cells.

Thus, its role in mediating cell entry has thus far been restricted to invasion across the gastrointestinal tract Jacquet et al. In contrast, InlB mediates entry into a wider variety of cells through binding to the more widely distributed cellular receptor Met, a protein kinase which is the ligand of endogenously produced hepatocyte growth factor. InlB also binds the globular portion of the receptor for the first component of complement C1q.

Binding either InlA or InlB protein to cells triggers intracellular signaling, although with some differences between them, that causes rearrangement of the cytoskeleton and internalization of bacteria Hamon et al.

Additionally, L. After entering a host cell, L. The mouse model of L. This model reasonably recapitulates the histological features of disease in humans and naturally infected animals.

However, as with any model, it has caveats and limitations. One is that immunocompetent mice are resistant to lethal infection and CNS invasion following gastrointestinal challenge with bacteria. At face value this might limit its role as a research tool given that the gastrointestinal route is the typical means by which humans are infected.

However a closer analysis suggests that this resistance towards developing severe systemic disease following a gut challenge also mimics the human situation. For example, recent epidemiological investigations show that ingestion of high bacterial inocula typically does not produce severe invasive disease in immunocompetent humans, but rather a self-limited febrile gastroenteritis. These outbreaks occurred in largely young and healthy populations and were linked to ingestion of contaminated chocolate milk c.

Although estimates of the amount of bacteria ingested were as high as 10 11 CFU per person in those who drank chocolate milk, these outbreaks produced no deaths or CNS infections and only one case of bacteremia.

Active case finding based on positive blood cultures identified three additional patients that were not associated with the initial epidemic but had consumed contaminated milk Dalton et al. This demonstrates that the absence of invasive disease in the original outbreak was not due to reduced bacterial virulence.

Mechanisms used by L. However, neuroinvasion can be achieved in a mouse model without genetic alteration. For example, Czuprynski , showed that the tendency for mice to develop CNS infection after gastric inoculation depends in part upon the strain of mouse as well as the strain of bacteria used.

Lastly, we showed that mice pharmacologically immunosuppressed with cyclosporin A and hydrocortisone, which mimics organ transplantation, readily developed CNS after inoculation via gastric lavage infection despite systemic treatment with gentamicin to kill extracellular bacteria Drevets et al. Collectively these data show that the mouse model is a reasonable mimic of the human situation with regard to the frequency of CNS invasion following gastrointestinal infection.

Nevertheless, most investigators favor parental inoculation of bacteria for the study of the mechanisms of CNS entry. In most clinical situations L. This is readily recapitulated in experimental L.

Bacteria injected intravenously. Systemic infection is marked by bacterial replication predominantly in the liver and spleen, and later also in the bone marrow de Bruijn et al.

Clearance mechanisms can be overwhelmed with large amounts of bacteria, e. However, in models in which lethal infection is produced using fewer bacteria, a secondary bacteremia develops and it is during this phase that bacteria enter the CNS Berche, ; Join-Lambert et al. Interestingly, our data show that the secondary bacteremia is composed of a combination of cell-free and intracellular bacteria Drevets, Furthermore, intracellular L. Kinetic analysis of organ infection following intravenous injection of Listeria monocytogenes.

Mice were injected intravenously with 4. CFU bacteria in the indicated organs were quantified by serial dilution and plating. Thus, they fit the broad definition of monocytes Ziegler-Heitbrock, ; Hume, In the mouse, the predominate subpopulations of monocytes are distinguished in part by variable expression of the Ly-6C antigen. Current data suggest that different subpopulations perform distinct roles in vivo.

For example, at steady state Ly-6C high monocytes show little trafficking to organs other than the spleen Geissmann et al. However, expression of CCR2 on Ly-6C high monocytes is thought to be crucial for mediating release of these cells from the bone marrow in response to chemokine ligands CCL2 or CCL7, and for directing them into acutely inflamed organs and spaces Geissmann et al.

By comparison, Ly-6C neg monocytes migrate into a variety of organs at steady state, possibly to perform homeostatic functions Geissmann et al. Acute L.

This is in accord with their role as the main monocyte subset that exits the bone marrow in response to peripheral demand Sunderkotter et al. Analyses of infection according to Ly-6C expression shows that both Ly-6C high and Ly-6C low monocytes are infected in vivo Drevets et al. However due to their greater representation Ly-6C high monocytes harbor the majority of cell-associated L. Listeria monocytogenes infection increases the percentage of Ly-6C high monocytes in the blood.

Blood was harvested from steady state mice and from mice infected 72 h prior with 2—4 LD 50 L. Leukocytes were labeled with the indicated mAb and were analyzed by flow cytometry. Dotplots show Ly-6C vs. Percentages of gated monocytes that are Ly-6C high at steady state and after infection are given.

Given the importance of parasitized monocytes, it is necessary to understand from where these cells originate as well as to identify where they go when they leave the circulation. As noted above, phenotypic similarities functional studies indicate that Ly-6C high monocytes are recent immigrants from the bone marrow. Similarly, recent studies show that the phenotype of infected monocytes in the peripheral blood is similar in many respects to that of monocytes in the bone marrow suggesting that L.

Literature review shows that L. Interestingly, data from de Bruijn showed that the bone marrow was sterile 1 h following intraperitoneal injection of a sublethal amount of L. This was confirmed by Join-Lambert and is illustrated by our data in Fig. These results show that the bone marrow does not simply filter bacteria from the bloodstream as do the liver and spleen and raises the question of how the bone marrow becomes infected. One possibility is that intracellular bacteria are transported within senescent neutrophils that home to the marrow after exiting heavily infected tissues Tacke et al.

Once in the bone marrow, the number of organisms increase rapidly for 72 h in sublethal infection then declines in concert with that observed in other organs, whereas in lethal infection there is unchecked replication de Bruijn et al.

The loss of neutrophils from the bone marrow partly explains its vulnerability to L. Additionally, it shows that cells which take up L. As reflected in the bloodstream, infection also skews the myeloid component of the bone marrow in favor of Ly-6C high CD31 pos myeloid precursors Fig. Specific changes induced by infection in the monocyte compartment, identified as Ly-6C high CD11b pos cells, include upregulation of both CD31 and CD11b which is contrary to the normal maturational pattern of increased surface expression of CD11b with decreased CD31 expression Leenen et al.

Listeria monocytogenes infection alters the phenotype of monocytic cells in the bone marrow. Bone marrow cells were harvested from steady state mice and from mice infected 72 h prior with 2—4 LD 50 L. Cells were labeled with the indicated mAb and were analyzed by flow cytometry. Contour plots show Ly-6C vs. CD31 a and Ly-6C vs.

CD11b b plots of total bone marrow cells. Percentages of cells in quadrants and in sort rectangles are shown. Percentages of CD31 positive cells are given. Electron microscopy identified bacteria within myeloid cells of both monocytic and granulocytic lineages in various stages of development.

These studies support the hypothesis that the organism parasitizes bone marrow myeloid cells. Further evidence for this parasitism comes from experiments in which gentamicin-treated mice are infected with L.

The presence of GFP-expressing bacteria within cells is a reliable marker for intracellular parasitism Fig. Collectively, this body of information demonstrates that bone marrow cells identified phenotypically and morphologically as Ly-6C hi CD31 pos CD11b pos monocyte precursors are a reservoir for L.

Interestingly, these cells are capable of establishing CNS infection when isolated from infected animals and inoculated into uninfected ones Join-Lambert et al. Thus, Ly-6C high CD11b pos monocytes are able to transport bacteria from the bone marrow to the bloodstream and from there into the brain. Monocytic cells in the bone marrow are parasitized by Listeria monocytogenes in vivo. Cells were analyzed and sorted by flowcytometry.

The arrowhead indicates bacteria. Mice were infected with 4. The hypothesis that infected phagocytes play a key role in establishing CNS infection by L. However, this histological study did not distinguish monocytes transporting bacteria into the brain from those recruited into it after infection was already established. To demonstrate that infected phagocytes are not mere bystanders, but rather are transporters of intracellular bacteria to the brain, cell-free bacteria were eliminated from the bloodstream during in vivo infection Drevets et al.

This was accomplished by treating mice with gentamicin, a bactericidal antibiotic that penetrates cells poorly, delivered by surgically implanted osmotic pumps. In these experiments, gentamicin-treated mice had fewer bacteria in the bloodstream than did untreated mice indicating that essentially all bacteria were cell-associated. Despite clearance of cell free bacteria, the gentamicin-treated mice developed brain infection to the same extent as did untreated mice.

Further evidence supporting the role of parasitized phagocytes in establishing CNS infection in mice comes from observations that bacterial infection of the brain by L. Studies for our laboratories show that Ly-6C high monocytes accumulate in the brains of systemically infected mice, although neutrophils do not, and that they harbor the majority of bacteria associated with CD11b pos cells in the brain Fig.

Additionally, infected monocytes have been observed adhering to the walls of brain capillaries and undergoing transmigration into the subarachnoid space Join-Lambert et al. Once infected phagocytes arrive at or in the CNS, in vitro data suggest that bacteria carried by them can enter parenchymal cells including endothelial cells and neurons by cell-to-cell spread or can be phagocytosed by microglia Drevets et al.

Ly-6C high monocytes are recruited to the brains of Listeria monocytogenes -infected mice and harbor bacteria. Brains were harvested from steady state mice or from mice 96 h after intravenous infection with c. Dot plots show gated CD11b pos cells from representative mice. What is not yet known are the mechanisms by which Ly-6C high monocytes are attracted to CNS during infection. A chemokine gradient enables directional migration of leukocytes expressing the cognate chemokine receptors.

The extent to which cell free L. In vitro studies from our laboratories and from others showed that L. However, experimental results showed that the invasion proteins, in particular InlB, did Greiffenberg et al. Discrepant results were later attributed to the finding that normal human serum contains antibodies that strongly inhibit L.

Thus, invasion of these microvascular cells in serum-free conditions in vitro is dependent upon InlB, but its role in vivo would be limited. Epidemiologic data in humans also suggest InlA does not contribute to CNS invasion from the bloodstream.

Jacquet analyzed protein expression of full-length internalin in clinical strains of L. The authors identified a statistically significant role for InlA in invasion across the gastrointestinal tract and for entering the placenta from the bloodstream. However, no significant correlation was established for the role of InlA for crossing into the CNS from the bloodstream. These data were recently recapitulated in the mouse by Wollert who constructed a L.

In vivo experiments showed that the LD 50 of bacteria expressing mutated InlA was c. The authors concluded that after the gastrointestinal tract is colonized and the intestinal epithelium is infected, dissemination of L.

In addition to neuroinvasion from the bloodstream, L. The neural route refers to a mechanism in which bacteria enter axons in the periphery then centripetally migrate within them into the brainstem. This process was identified by finding L. Several investigators have experimentally recapitulated this by inoculation of bacteria into oral and ocular tissues of goats and mice, or by direct injection into peripheral neurons Asahi et al.

In vitro experiments by several different investigators evaluated the ability of L. These studies revealed that non-neuronal cells take up bacteria more avidly than do neurons, with microglia being the most easily infected.

In contrast, binding and invasion of neurons occurs to some extent and is probably internalin-independent, but the frequency by which it happens is quite variable depending upon the origin of the neurons, how they are cultured, and how bacterial infection is measured Dramsi et al.

A more reliable means for L. Importantly, a key role for macrophages in facilitating neural invasion in vivo was established by Jin who showed that L. Collectively these data provide a clearer understanding of the neural route of invasion in animals and a mechanism by which these cells can be infected, but the applicability to human infection remains unclear. Recently, however, careful analysis of autopsy material from nine humans who died of brainstem encephalitis revealed inflammatory infiltrates within nuclei, tracts, and intra-parenchymal parts of cranial nerves V, VII, IX, X, and XII, which innervate different areas of the oropharynx Antal et al.

This number is considerably higher than previously reported and needs to be considered in light of the difficulties of making a retrospective diagnosis of brainstem encephalitis in the absence of modern imaging techniques, e. Nonetheless, it suggests that humans as well as ruminants are attacked by the neural route of CNS invasion.

There have been many exciting new developments in the study of L. Certainly many questions remain to be answered and many yet to be asked. Regarding clinical disease and at-risk populations, there may be polymorphisms in key immune response genes that contribute to the susceptibility of seemingly healthy individuals to severe L. Because monocytes have dual roles in the pathogenesis of L. For example, it is not fully understood how bone marrow monocytes first become infected or why these cells are susceptible to intracellular infection rather than being able to kill the bacteria.

The mechanisms by which infected monocytes are recruited to and enter the CNS have yet to be elucidated. Additionally, given the mismatch between human and murine E-cadherin, are there other differences between mice and humans that influence the means by which L.

One of the strengths of experimental L. Thus, one of the key questions to be answered is to what extent does L. For example, recent data show that Toxoplasma gondii enters the brain within parasitized CD11b pos monocytes Courret et al. In this respect, it will be important to understand the importance of pathogen-specific features relative to commonalities in the host responses to them.

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