Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004623 (bacterial infection)
 15,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cells display a distinct spatial distribution in the lung where they are found preferentially in intraepithelial locations or in deeper tissue around blood vessels, bronchioles and mucus secreting glands. Yet the physiological role of these granule-laden cells is unknown. There are now intriguing signs that their distinctive distribution together with their intrinsic capacity to release large amounts of inflammatory mediators serve a critical role in immune surveillance. Mast cells have now been shown to be capable of recognizing and aggressively reacting to a wide range of bacteria. The mast cell responses involve ingesting and killing of adherent bacteria, in a manner not unlike that of traditional phagocytic cells. Concomitant with this endocytic activity, a large variety of potent inflammatory mediators are released by the mast cell. One such mast cell-derived mediator, TNF-alpha, was recently shown to be a critical signal for initiating neutrophil influx to sites of bacterial infection in the lung as well as the peritoneum of mice. This capacity of mast cells to recruit neutrophils, together with its recently reported participation in processing and presenting bacterial antigens to immune cells and in mediating proliferation of epithelial cells and mucosal mucus secretion, indicate that mast cells have an extraordinary ability to modulate the innate as well as adaptive immune responses to infectious microorganisms.
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PMID:Mast cells as modulators of host defense in the lung. 915 15

The anaphylatoxin C5a has been implicated in the pathogenesis of bacterial meningitis as a potent mediator of inflammation in the subarachnoid space. We investigated the expression of the receptor for C5a (C5aR) in brains of mice with experimental Listeria monocytogenes (LM) meningoencephalitis. In the course of the disease, infiltrating cells in the meninges and the ventricles were found to express C5aR mRNA and protein. In the brain parenchyma, very low constitutive C5aR expression was seen on pyramidal neurons and Purkinje cells. However, in LM-infected mice, a dramatic increase in C5aR expression occurred on neurons starting 6 h after infection and was maximal between 24 and 36 h. TNF-alpha was identified as an essential mediator of neuronal C5aR expression, since mice lacking the genes for TNF and lymphotoxin-alpha (TNF/lymphotoxin-alpha -/- mice) showed significantly attenuated C5aR expression after LM infection. Furthermore, i.p. injection of recombinant TNF-alpha induced enhanced C5aR expression in the brains of TNF/lymphotoxin-alpha -/- mice and in normal animals even in the absence of a bacterial infection. We also assessed the levels of anaphylatoxin C5a in the cerebrospinal fluid of patients with infectious meningitis. C5a was detected in all patients with bacterial meningitis (n = 9), in 6 of 18 patients with aseptic meningitis, and in 1 of 66 control patients. The finding of TNF-alpha-mediated C5aR expression on neurons in experimental Listeria meningitis and the detection of the ligand, C5a, in the cerebrospinal fluid of human patients with infectious meningitis present new directions in the investigation of the pathophysiologic sequelae leading to secondary brain damage.
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PMID:TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis. 921 5

We studied the effects of M-CSF on cytokine induction in vivo by LPS or by bacterial infection by comparing between the serum cytokine levels of mice administered with and without M-CSF. M-CSF at 250 micrograms/kg/day for 3 days significantly augmented serum IL-6 level induced by a subsequent injection of 25 micrograms/kg of LPS. The augmented IL-6-induction was dose-dependent from 50 to 1250 micrograms/kg/day of M-CSF, and required 2- to 3-doses of M-CSF at 250 micrograms/kg/day. Mice primed with M-CSF induced IL-6 in response to a 5-fold lower dose of LPS, and also produced higher levels of IL-1 alpha, IL-10, GM-CSF, TNF-alpha, and IFN-gamma than control mice. The priming effect of M-CSF was transient and reversible, and elicited independently of T-cells. An injection with intact bacteria, such as Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus also induced IL-6 in normal mice, and M-CSF administration augmented the induction of these cytokines. These results showed that M-CSF positively regulates LPS-dependent and -independent cytokine induction, suggesting a defensive effect against infectious agents through enhanced cytokine production.
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PMID:Macrophage colony-stimulating factor (M-CSF) augments cytokine induction by lipopolysaccharide (LPS)-stimulation and by bacterial infections in mice. 928 40

Chronic bone infection, as attends periodontitis, is often complicated by severe osteolysis. While LPS is believed to be central to the pathogenesis of the osteolytic lesion, the mechanisms by which this bacteria-derived molecule promotes bone resorption are unknown. We find that LPS induces bone marrow macrophages (BMMs) to express c-src, a protooncogene product that we demonstrate is a specific marker of commitment to the osteoclast phenotype. We next turned to possible soluble mediators of LPS-induced c-src. Of a number of osteoclastogenic cytokines tested, only TNF-alpha mirrors the c-src-enhancing effect of LPS. Suggesting that LPS augmentation of c-src is TNF-mediated, endotoxin sequentially induces BMM expression of TNF, followed by c-src. TNF and c-src expression, by cultured BMMs derived from LPS-injected mice, reflects duration of exposure to circulating endotoxin, intimating that endotoxin's effect in vivo is also mediated by TNF. Consistent with these findings, thalidomide (which antagonizes TNF action) attenuates c-src induction by LPS. An anti-TNF antibody blocks LPS enhancement of c-src mRNA, validating the cytokine's modulating role in vitro. Using BMMs of TNF receptor-deleted mice, we demonstrate that TNF induction of c-src is transmitted through the cytokine's p55, but not p75, receptor. Most importantly, LPS administered to wild-type mice prompts osteoclast precursor differentiation, manifest by profound osteoclastogenesis in marrow cultured ex vivo, and by a profusion of marrow-residing cells expressing the osteoclast marker tartrate resistant acid phosphatase, in vivo. In contrast, LPS does not substantially enhance osteoclast proliferation in mice lacking the p55TNF receptor, confirming that LPS-induced osteoclastogenesis is mediated by TNF in vivo via this receptor. Thus, therapy targeting TNF and/or its p55 receptor presents itself as a means of preventing the osteolysis of chronic bacterial infection.
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PMID:Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor. 929 24

Use of murine listeriosis as an experimental model has greatly increased our understanding of the complex interplay of cells and mediators in non-specific antibacterial resistance (innate immunity). Important contributions made with this experimental model include demonstrating the ability of inflammatory cytokines (i.e. IFN-gamma, IL-1 alpha, TNF-alpha) to protect against bacterial infection, and illustrating the rapidity of the host cytokine response (detectable within 1 h of challenge) during bacterial infection. Most experimental studies of host defense against Listeria monocytogenes (L. monocytogenes) have used a parenteral challenge (i.v. or i.p.). This ignores the pathogenesis of naturally occurring listeriosis, which usually results from ingestion of Listeria-contaminated food products. In this review, we will include consideration of the host-pathogen interactions that occur when L. monocytogenes invades through its natural portal of entry, the gastrointestinal tract. Although resistance to facultative intracellular pathogens, such as L. monocytogenes, was formerly thought to revolve exclusively around the T helper cell/macrophage axis, more recent evidence indicates that neutrophils are able to ingest and kill L. monocytogenes and prevent the unrestricted multiplication of listeriae in parenchymal cells. Exploring the mechanisms involved in this process will provide new insights into the communication between leukocytes and tissue cells in host defense.
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PMID:Non-specific resistance mechanisms to listeriosis: implications for experimental and naturally occurring infection. 931 73

During systemic infection, the serum lipopolysaccharide binding protein (LBP) binds to the lipid A component of bacterial endotoxins and facilitates its delivery to the CD 14 receptor on the cell surface of macrophages, where proinflammatory cytokines are released. There is no knowledge to date whether LBP is also present in the effluent of patients with continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis. We investigated the dialysis effluent of 37 patients with CAPD peritonitis for immunoreactive LBP, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 beta and compared the findings with the cytokine levels in 20 noninfected CAPD patients. The mean +/- SEM concentrations of LBP, TNF-alpha, and IL-1 beta were significantly higher in the effluent of patients with peritonitis than in noninfected CAPD effluent. In comparison to controls (0.23 +/- 0.05 microgram/mL), LBP was 0.68 +/- 0.13 microgram/mL in the effluent of patients with CAPD-associated infectious peritonitis. For TNF-alpha, levels were 0.50 +/- 0.25 pg/mL in the control effluent versus 124.7 +/- 46.6 pg/mL in the effluent of peritonitis patients. For IL-1 beta the levels were 0.24 +/- 0.14 pg/mL in the control effluent and 71.23 +/- 17.53 pg/mL in the peritonitis patients. Our findings demonstrate that LBP is significantly elevated in the effluent of CAPD patients during an episode of CAPD-associated peritonitis and might be used as a marker of intraperitoneal bacterial infection.
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PMID:Lipopolysaccharide binding protein: a marker for intraperitoneal bacterial infection in patients with CAPD peritonitis. 936 Jun 83

This study investigated the effect of naturally acquired bacterial infection of the bovine mammary gland on subpopulations of T lymphocytes and cytokine expression in milk. Twenty-nine lactating cows with mastitis were compared to 12 normal animals. CD4+ lymphocytes represented a significantly greater percentage of the milk-derived lymphocytes in infected mammary glands compared to normal controls. Cytokine mRNA expression by cells derived from milk was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR). No IL-2 or IL-4 mRNA was detected in any samples, while IFN-gamma mRNA was detected in all milk samples. IL-10 mRNA was detected in cells from the milk of 2 mastitic cows and 1 normal cow, and IL-12 mRNA was detected in 2 cows with mastitis. While TNF-alpha mRNA was not detected in this study, IL-6 mRNA was identified in cells from the milk of all animals, with levels being greater in mastitic animals.
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PMID:T cell populations and cytokine expression in milk derived from normal and bacteria-infected bovine mammary glands. 942 11

LPS-binding protein (LBP) recognizes bacterial LPS and transfers it to CD14, thereby enhancing host cell stimulation, eventually resulting in pathogenic states such as septic shock. Recently, LBP also was shown to detoxify LPS by transferring LPS into HDL particles in vitro. Thus, the predominant in vivo function of LBP has remained unclear. To investigate the biological activity of acute phase concentrations of recombinant murine LBP, high concentrations of LBP were investigated in vitro and in vivo. Although addition of low concentrations of LBP to a murine macrophage cell line enhanced LPS-induced TNF-alpha synthesis, acute phase concentrations of LBP blocked this effect in comparison to low-dose LBP. When injected into mice intraperitoneally, LBP inhibited LPS-mediated cytokine release and prevented hepatic failure resulting in a significantly decreased mortality rate in LPS-challenged and D-galactosamine-sensitized mice, as well as in a murine model of bacteremia. These results complement a recent study revealing LBP-deficient mice to be dramatically more susceptible to an intraperitoneal Salmonella infection as compared with normal mice. We conclude that acute phase LBP has a protective effect against LPS and bacterial infection and may represent a physiologic defense mechanism against infection. Despite the limitations of any murine sepsis model, the results shown may imply that LBP could have beneficial effects during gram-negative peritonitis in humans.
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PMID:LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria. 959 62

Although recent findings indicate that gamma delta T cells influence both early innate and Ag-specific adaptive host responses, it has remained unclear what triggers gamma delta T cell reactivity. Investigating very early T cell activation in mouse and human models of bacterial infection, we measured CD69 expression as an indicator of early cellular activation. Both murine alpha beta and gamma delta T cells responded polyclonally to systemic bacterial infections, and to LPS. However, gamma delta T cells responded more strongly to the bacteria and to LPS. In vitro LPS-stimulated human T cells showed a similar differential response pattern. We identified TNF-alpha as mediator of the early differential T cell activation, and of differential proliferative responses. The stronger response of gamma delta T cells to TNF-alpha was correlated with higher inducible expression levels of TNF-Rp75. Among unstimulated splenocytes, more gamma delta T cells than alpha beta T cells expressed CD44 at high levels. The data suggest that TNF-Rp75 determines the differential T cell reactivity, and that most gamma delta T cells in the normal spleen are present in a presensitized state. As TNF-alpha stimulates activated T cells, it may early preferentially connect gamma delta T cell functions with those of cells that produce this cytokine, including activated innate effector cells and Ag-stimulated T lymphocytes.
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PMID:Early preferential stimulation of gamma delta T cells by TNF-alpha. 960 17

Cystic fibrosis (CF) is an inherited disorder associated with severe inflammation and repeated bacterial infection and colonization in the lung. Airway epithelium is involved in defence against bacteria, but this system may be defective in CF. Pro-inflammatory cytokines can stimulate the expression of inducible nitric oxide synthase (iNOS), an enzyme generating nitric oxide, which functions as an important mediator in host defence mechanisms. To understand better the poor resistance to infections in the CF lung, the expression of the iNOS gene was investigated in explanted lungs from patients with cystic fibrosis (n = 13), bronchiectasis (n = 3), emphysema (n = 14), and in normal lungs (n = 8). In addition, bronchial epithelial cell lines were examined to study iNOS gene expression in vitro. Strong immunoreactivity for iNOS was seen in inflammatory cells and bronchial epithelium in all the diseased lungs, except for bronchial epithelium in CF. Quantitative analysis showed a significant reduction in the area of epithelium immunostained in CF [CF 6.8 +/- 1.6 (% +/- SEM); emphysema 18.2 +/- 2.8; normal 9.6 +/- 0.8, P < 0.01], regardless of steroid treatment. These results were supported by in situ hybridization of iNOS mRNA, which showed a pattern of gene expression in CF, emphysema, and normal lung which paralleled that of protein immunoreactivity. Stimulation with cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) increased the expression of iNOS mRNA detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in cultures of normal (16HBE14o-), but not CF (CFBE41o-, with delta F508 CFTR mutation) epithelial cells. Expression of iNOS in inflammatory cells suggests that the gene is normal in CF. Absence of iNOS from bronchial epithelium may be due to low expression of the gene resulting from abnormalities in the signalling system that normally causes induction, such as cytokine receptors, second messengers or transcription factors. The resulting deficiency of the nitric oxide defence system may be relevant to the susceptibility of CF patients to pulmonary bacterial colonization.
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PMID:Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis. 961 86


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