Infection of central nervous system by motile Enterococcus: first case report.
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A 66-year-old man with four indwelling ventriculoperitoneal shunts for multiloculated hydrocephalus from a complicated case of meningitis a year before developed shunt infection based on a syndrome of fever, drowsiness, and cerebrospinal fluid neutrophil pleocytosis in the background of repeated surgical manipulation to relieve successive shunt blockages. The cerebrospinal fluid culture, which yielded a motile Enterococcus species, was believed to originate from the gut. This isolate was lost in storage and could not be characterized further. The patient improved with vancomycin and high-dose ampicillin therapy. He relapsed a month later with Enterococcus gallinarum shunt infection, which responded to high-dose ampicillin and gentamicin therapy. This is probably the first case report of motile Enterococcus infection of the central nervous system. (+info)
Listeria monocytogenes-infected phagocytes can initiate central nervous system infection in mice.
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Listeria monocytogenes-infected phagocytes are present in the bloodstream of experimentally infected mice, but whether they play a role in central nervous system (CNS) invasion is unclear. To test whether bacteria within infected leukocytes could establish CNS infection, experimentally infected mice were treated with gentamicin delivered by surgically implanted osmotic pumps. Bacterial inhibitory titers in serum and plasma ranged from 1:16 to 1:256, and essentially all viable bacteria in the bloodstream of treated mice were leukocyte associated. Nevertheless, CNS infection developed in gentamicin-treated animals infected intraperitoneally or by gastric lavage, suggesting that intracellular bacteria could be responsible for neuroinvasion. This was supported by data showing that 43.5% of bacteria found with blood leukocytes were intracellular and some colocalized with F-actin, indicating productive intracellular parasitism. Experiments using an L. monocytogenes strain containing a chromosomal actA-gfpuv-plcB transcriptional fusion showed that blood leukocytes were associated with intracellular and extracellularly bound green fluorescent protein-expressing (GFP+) bacteria. Treatment with gentamicin decreased the numbers of extracellularly bound GFP+ bacteria significantly but did not affect the numbers of intracellular GFP+ bacteria, suggesting that the latter were the result of intercellular spread of GFP+ bacteria to leukocytes. These data demonstrate that infected leukocytes and the intracellular L. monocytogenes harbored within them play key roles in neuroinvasion. Moreover, they suggest that phagocytes recruited to infected organs such as the liver or spleen are themselves parasitized by intercellular spread of L. monocytogenes and then reenter the bloodstream and contribute to the systemic dissemination of bacteria. (+info)
Effect of deficiency of tumor necrosis factor alpha or both of its receptors on Streptococcus pneumoniae central nervous system infection and peritonitis.
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Tumor necrosis factor alpha (TNF-alpha) and TNF-beta are key mediators in bacterial inflammation. We therefore examined the role of TNF-alpha and its two receptors in murine pneumococcal central nervous system infection. TNF-alpha knockout mice and age- and sex-matched controls and TNF receptor (p55 and p75)-deficient mice and heterozygous littermates were infected intracerebrally with a Streptococcus pneumoniae type 3 strain. Mice were monitored until death or were killed 36 h after infection. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration and neuronal damage were assessed by histological scores. TNF-alpha-deficient mice died earlier than the controls after intracerebral infection although overall survival was similar. TNF-alpha deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in brain homogenates. However, it caused a substantial rise of the concentration of S. pneumoniae cells in blood and spleen. Spleen bacterial titers were also increased in p55- and p75-deficient mice. TNF receptor-deficient mice showed decreased meningeal inflammation. Neuronal damage was not affected by either TNF-alpha or TNF receptor deficiency. In a murine model of pneumococcal peritonitis, 10(2) CFU of S. pneumoniae produced fatal peritonitis in TNF-alpha-deficient, but not wild-type, mice. Early leukocyte influx into the peritoneum was impaired in TNF-alpha-deficient mice. The lack of TNF-alpha or its receptors renders mice more susceptible to S. pneumoniae infections. (+info)
Bacterial lipopolysaccharide selectively up-regulates the function of the chemotactic peptide receptor formyl peptide receptor 2 in murine microglial cells.
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Receptors for the bacterial chemotactic peptide fMLP are implicated in inflammation and host defense against microbial infection. We investigated the expression and function of fMLPR in microglial cells, which share characteristics of mononuclear phagocytes and play an important role in proinflammatory responses in the CNS. The expression of the genes encoding formyl peptide receptor (FPR)1 and FPR2, the high- and low-affinity fMLPR, was detected in a murine microglial cell line N9, but these cells did not respond to chemotactic agonists known for these receptors. N9 cells incubated with bacterial LPS increased the expression of fMLPR genes and developed a species of specific, but low-affinity, binding sites for fMLP, in association with marked calcium mobilization and chemotaxis responses to fMLP in a concentration range that typically activated the low-affinity receptor FPR2. In addition, LPS-treated N9 cells were chemoattracted by two FPR2-specific agonists, the HIV-1 envelope-derived V3 peptide, and the 42 aa form of the amyloid beta peptide which is a pathogenic agent in Alzheimer's disease. Primary murine microglial cells also expressed FPR1 and FPR2 genes, but similar to N9 cells, exhibited FPR2-mediated activation only after LPS treatment. In contrast to its effect on the function of FPR2, LPS reduced N9 cell binding and biological responses to the chemokine stromal cell-derived factor-1alpha. Thus, LPS selectively modulates the function of chemoattractant receptors in microglia and may promote host response in inflammatory diseases in the CNS. (+info)
Chlamydia pneumoniae infection of the central nervous system worsens experimental allergic encephalitis.
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Experimental allergic encephalitis (EAE) is considered by many to be a model for human multiple sclerosis. Intraperitoneal inoculation of mice with Chlamydia pneumoniae, after immunization with neural antigens, increased the severity of EAE. Accentuation of EAE required live infectious C. pneumoniae, and the severity of the disease was attenuated with antiinfective therapy. After immunization with neural antigens, systemic infection with C. pneumoniae led to the dissemination of the organism into the central nervous system (CNS) in mice with accentuated EAE. Inoculation with Chlamydia trachomatis did not worsen EAE and infectious organisms were not seen in the CNS. These observations suggest that dissemination of C. pneumoniae results in localized infection in CNS tissues in animals with EAE. We propose that infection of the CNS by C. pneumoniae can amplify the autoreactive pool of lymphocytes and regulate the expression of an autoimmune disease. (+info)
Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease.
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Activated microglia, the resident macrophages of the brain, are a feature of Alzheimer's disease. Animal models suggest that when activated microglia are further activated by a subsequent systemic infection this results in significantly raised levels of interleukin 1beta within the CNS, which may in turn potentiate neurodegeneration. This prospective pilot study in Alzheimer's disease subjects showed that cognitive function can be impaired for at least two months after the resolution of a systemic infection and that cognitive impairment is preceded by raised serum levels of interleukin 1beta. These relations were not confounded by the presence of any subsequent systemic infection or by baseline cognitive scores. Further research is needed to determine whether recurrent systemic infections drive cognitive decline in Alzheimer's disease subjects through a cytokine mediated pathway. (+info)
Cultivation of Tropheryma whipplei from cerebrospinal fluid.
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Whipple disease (WD) is a systemic disorder caused by the bacterium Tropheryma whipplei. Since the recognition of a bacterial etiology in 1961, many attempts have been made to cultivate this bacterium in vitro. It was eventually isolated, in 2000, from an infected heart valve, in coculture with human fibroblasts. Here we report the isolation of 2 new strains of T. whipplei from cerebrospinal fluid (CSF) of 2 patients with intestinal WD but no neurological signs or symptoms. One culture-positive specimen was obtained before treatment; the other was obtained 12 months after discontinuation of therapy, at a time of intestinal remission. In both cases, 15 passages of the cultures were completed over 17 months. Bacterial growth was measured by quantitative polymerase chain reaction, which suggested a generation time of 4 days. Staining with YO-PRO nucleic-acid dye showed characteristic rod-shaped bacteria arranged in chains. Fluorescent in situ hybridization with a T. whipplei-specific oligonucleotide probe, a broad-range bacterial probe, and a nonspecific nucleic-acid stain indicated that all visible bacteria were T. whipplei. Scanning electron microscopy and transmission electron microscopy showed both intracellular and extracellular bacteria. This first isolation of T. whipplei from CSF provides clear evidence of viable bacteria in the central nervous system in individuals with WD, even after prolonged antibiotic therapy. (+info)
Invasion of the central nervous system by intracellular bacteria.
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Infection of the central nervous system (CNS) is a severe and frequently fatal event during the course of many diseases caused by microbes with predominantly intracellular life cycles. Examples of these include the facultative intracellular bacteria Listeria monocytogenes, Mycobacterium tuberculosis, and Brucella and Salmonella spp. and obligate intracellular microbes of the Rickettsiaceae family and Tropheryma whipplei. Unfortunately, the mechanisms used by intracellular bacterial pathogens to enter the CNS are less well known than those used by bacterial pathogens with an extracellular life cycle. The goal of this review is to elaborate on the means by which intracellular bacterial pathogens establish infection within the CNS. This review encompasses the clinical and pathological findings that pertain to the CNS infection in humans and includes experimental data from animal models that illuminate how these microbes enter the CNS. Recent experimental data showing that L. monocytogenes can invade the CNS by more than one mechanism make it a useful model for discussing the various routes for neuroinvasion used by intracellular bacterial pathogens. (+info)