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)

Asphalt fume inhalation has been suspected of affecting immune function in exposed workers. The objective of this study was to evaluate the effect of asphalt exposure on lung immune responses in rats using a bacterial infectivity model. Pathogen-free male Sprague-Dawley rats were exposed by inhalation to asphalt fumes (72.6 +/- 4.95 mg/m3) or filtered air for 6 h/day for 5 days. One day after the final asphalt exposure, rats were intratracheally inoculated with 5 x 10(5) Listeria monocytogenes. At 0 (prior to bacterial inoculation), 3, and 7 days after L. monocytogenes instillation, the lungs of each animal were divided. Bronchoalveolar lavage (BAL) was performed on right lungs. The recovered BAL cells were then differentiated and counted, and alveolar macrophage (AM) function was determined. Albumin and lactate dehydrogenase (LDH), two indices of lung injury, were measured in the acellular BAL fluid. To assess bacterial clearance, the left lungs were removed, homogenized, and bacterial colony-forming units (CFUs) were counted. In addition, lung-draining lymph nodes were removed, and lymphocyte phenotype and lymphocyte-induced cytokine production were examined. Asphalt fume exposure did not cause lung injury or inflammation in rats in the absence of infection. Infection induced elevations in AMs, neutrophils (PMNs), albumin, and LDH. Importantly, no significant differences were seen when comparing the asphalt group with the air and nonexposed naive groups at any time before or after infection. Also, asphalt fume inhalation exposure did not affect the rate of pulmonary clearance of L. monocytogenes or AM production of reactive oxygen and nitrogen species. However, asphalt-related increases in lymphocyte secretion of interferon (IFN)-gamma, interleukin (IL)-6, and IL-10 were observed at different times after bacterial infection, whereas the total number of lymph-node cells and the percentage of CD4+ and CD8+ cells were not significantly different among the treatment groups. Despite the asphalt-induced changes observed in lymphokine secretion, adaptive immune function seemed to function properly in lung defense against bacterial infection. Because innate nonspecific lung responses and pulmonary clearance of L. monocytogenes were unaffected by asphalt fume exposure, lung defenses were sufficient to control the infection. It was concluded that acute inhalation of asphalt fumes at a high concentration had a minimal effect on lung immune responses to infection in rats.
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PMID:Effect of asphalt fume inhalation exposure at simulated road paving conditions prior to bacterial infection on lung defense responses in rats. 1456 97

Diesel exhaust particles (DEP) have been shown to alter pulmonary immune responses to bacterial infection. Exposure of rats to 100 mg/m(3) DEP for 4 h was found to aggravate Listeria monocytogenes(Listeria) infection at 3 days postinfection, but the bacteria were largely cleared at 7 days postinfection due to the development of a strong T cell-mediated immunity. In the present study, we examined the effects of repeated DEP exposure at lower doses on pulmonary responses to bacterial infection. Brown Norway rats were exposed to DEP by inhalation at 20.62 +/- 1.31 mg/m 3 for 4 h/day for 5 days, followed by intratracheal inoculation with 100,000 Listeria at 2 h after the last DEP exposure. DEP-exposed rats showed a significant increase in lung bacterial load at both 3 and 7 days postinfection. The repeated DEP exposure was shown to suppress both the innate, orchestrated by alveolar macrophages (AM), and T cell-mediated responses to Listeria. DEP inhibited AM production of interleukin- (IL-) 1beta, tumor necrosis factor- (TNF-) alpha, and IL-12 but enhanced Listeria-induced AM production of IL-10, which has been shown to prolong the survival of intracellular pathogens such as Listeria. DEP exposure also suppressed the development of bacteria-specific lymphocytes from lung-draining lymph nodes, as indicated by the decreased numbers of T lymphocytes and their CD4(+) and CD8(+) subsets. Furthermore, the DEP exposure markedly inhibited the Listeria-induced lymphocyte secretion of IL-2 at day 7, IL-10 at days 3 and 7, and interferon- (IFN-) gamma at days 3 to 10 postinfection when compared to air-exposed controls. These results show a sustained pattern of downregulation of T cell-mediated immune responses by repeated low-dose DEP exposure, which is different from the results of a single high-dose exposure where the acute effect of DEP aggravated bacteria infection but triggered a strong T cell-mediated immunity.
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PMID:Suppression of cell-mediated immune responses to listeria infection by repeated exposure to diesel exhaust particles in brown Norway rats. 1465 13

Periapical granulomas are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. In previous studies we have reported that the bone resorption in this model is primarily mediated by macrophage-expressed interleukin-1 (IL-1). The expression and activity of IL-1 is in turn modulated by a network of Th1 and Th2 regulatory cytokines. In the present study, the functional roles of the Th1 cytokine gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines IL-12 and IL-18 were determined in a murine model of periapical bone destruction. IL-12-/-, IL-18-/-, and IFN-gamma-/- mice were subjected to surgical pulp exposure and infection with a mixture of four endodontic pathogens, and bone destruction was determined by microcomputed tomography on day 21. The results indicated that all IL-12-/-, IL-18-/-, and IFN-gamma-/- mice had similar infection-stimulated bone resorption in vivo as wild-type control mice. Mice infused with recombinant IL-12 also had resorption similar to controls. IFN-gamma-/- mice exhibited significant elevations in IL-6, IL-10, IL-12, and tumor necrosis factor alpha in lesions compared to wild-type mice, but these modulations had no net effect on IL-1alpha levels. Recombinant IL-12, IL-18, and IFN-gamma individually failed to consistently modulate macrophage IL-1alpha production in vitro. We conclude that, at least individually, endogenous IL-12, IL-18, and IFN-gamma do not have a significant effect on the pathogenesis of infection-stimulated bone resorption in vivo, suggesting possible functional redundancy in proinflammatory pathways.
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PMID:Gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines interleukin-12 (IL-12) and IL-18 do not augment infection-stimulated bone resorption in vivo. 1471 54

Differentiation of hematopoietic stem cells (HSCs) can be influenced by different stimuli, including cytotoxic agents, certain cytokines, and contact with pathogens. Infection may result in dysregulation of these important progenitor cells and therefore interfere with the availability of blood cells. In this study we analyzed the effect of bacterial infection on HSCs concerning surface marker expression and cytokine release. Listeria monocytogenes and Yersinia enterocolitica accelerated maturation of hematopoietic progenitor cells along the myeloid lineage, as demonstrated by the upregulation of CD13, CD14, and costimulatory signals. By screening cytokine secretion, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-6, IL-8, IL-10, IL-12, and tumor necrosis factor-alpha were found to be induced by bacterial infection. These data indicate that infection of HSCs with L. monocytogenes and Y. enterocolitica affects the differentiation of CD34(+) hematopoietic progenitors in vitro and may lead to secretion of cytokines that can influence the HSC differentiation capacity and immune response.
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PMID:Bacterial infection of human hematopoietic stem cells induces monocytic differentiation. 1498 33

Macrophages (Mphi) play a central role as effector cells in immunity to intracellular pathogens such as Mycobacterium. Paradoxically, they also provide a habitat for intracellular bacterial survival. This paradoxical role of Mphi remains poorly understood. Here we report that this dual role may emanate from the functional plasticity of Mphi: Whereas Mphi-1 polarized in the presence of granulocyte-Mphi colony-stimulating factor promoted type 1 immunity, Mphi-2 polarized with Mphi colony-stimulating factor subverted type 1 immunity and thus may promote immune escape and chronic infection. Importantly, Mphi-1 secreted high levels of IL-23 (p40/p19) but no IL-12 (p40/p35) after (myco)bacterial activation. In contrast, activated Mphi-2 produced neither IL-23 nor IL-12 but predominantly secreted IL-10. Mphi-1 required IFN-gamma as a secondary signal to induce IL-12p35 gene transcription and IL-12 secretion. Activated dendritic cells produced both IL-12 and IL-23, but unlike Mphi-1 they slightly reduced their IL-23 secretion after addition of IFN-gamma. Binding, uptake, and outgrowth of a mycobacterial reporter strain was supported by both Mphi subsets, but more efficiently by Mphi-2 than Mphi-1. Whereas Mphi-1 efficiently stimulated type 1 helper cells, Mphi-2 only poorly supported type 1 helper function. Accordingly, activated Mphi-2 but not Mphi-1 down-modulated their antigen-presenting and costimulatory molecules (HLA-DR, CD86, and CD40). These findings indicate that (i) Mphi-1 and Mphi-2 play opposing roles in cellular immunity and (ii) IL-23 rather than IL-12 is the primary type 1 cytokine produced by activated proinflammatory Mphi-1. Mphi heterogeneity thus may be an important determinant of immunity and disease outcome in intracellular bacterial infection.
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PMID:Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. 1507 Jul 57

Secondary pneumococcal pneumonia is a serious complication during and shortly after influenza infection. We established a mouse model to study postinfluenza pneumococcal pneumonia and evaluated the role of IL-10 in host defense against Streptococcus pneumoniae after recovery from influenza infection. C57BL/6 mice were intranasally inoculated with 10 median tissue culture infective doses of influenza A (A/PR/8/34) or PBS (control) on day 0. By day 14 mice had regained their normal body weight and had cleared influenza virus from the lungs, as determined by real-time quantitative PCR. On day 14 after viral infection, mice received 10(4) CFU of S. pneumoniae (serotype 3) intranasally. Mice recovered from influenza infection were highly susceptible to subsequent pneumococcal pneumonia, as reflected by a 100% lethality on day 3 after bacterial infection, whereas control mice showed 17% lethality on day 3 and 83% lethality on day 6 after pneumococcal infection. Furthermore, 1000-fold higher bacterial counts at 48 h after infection with S. pneumoniae and, particularly, 50-fold higher pulmonary levels of IL-10 were observed in influenza-recovered mice than in control mice. Treatment with an anti-IL-10 mAb 1 h before bacterial inoculation resulted in reduced bacterial outgrowth and markedly reduced lethality during secondary bacterial pneumonia compared with those in IgG1 control mice. In conclusion, mild self-limiting influenza A infection renders normal immunocompetent mice highly susceptible to pneumococcal pneumonia. This increased susceptibility to secondary bacterial pneumonia is at least in part caused by excessive IL-10 production and reduced neutrophil function in the lungs.
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PMID:IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection. 1518 40

Induction of IDO is also under strict control by the immune system and we have previously shown that there are a number of cytokines involved in the down-regulation of IDO induction. In clinical practice anti-inflammatory substances and antibiotics are commonly used and may influence the outcome of bacterial infection. We analysed the IFNgamma-dependant IDO induction and bacteriostasis of Staphylococcus aureus and Group A Streptococcus (GAS) in monocyte-derived-macrophages (MDM) from cord blood and peripheral blood of healthy adult donors with attention to the effect of down-regulatory cytokines and of two commonly used anti-inflammatory agents, hydrocortisone and indomethacin, on both IDO activity and bacterial growth. In addition to this we were interested in the effect of sub-inhibitory concentrations of the antibiotic ampicillin on this IDO-mediated effect, the premise being that for a substantial period of antibiotic therapy the infection site is exposed to sub-inhibitory concentrations of antibiotic. We found that after stimulation with IFNgamma, MDM inhibited streptococcal growth. This was due to IFNgamma-induced IDO activity as demonstrated by reconstitution of growth by supplemental tryptophan. This IDO-mediated bacteriostasis was inhibited by the cytokines IL-10, IL-4 and TGFbeta. Furthermore, addition of indomethacin to IFNgamma stimulated MDM also resulted in the abrogation of the IDO-induced bacteriostasis, a result of the inhibition of IDO induction. Surprisingly, co-stimulation with hydrocortisone and IFNgamma apparently increased the IDO activity in cord blood MDM, but had no effect on the IDO-activity of adult peripheral blood MDM. Bacteriostasis in cord blood MDM, on the other hand, was not affected by co-stimulation with hydrocortisone. Ampicillin, in sub-inhibitory concentrations had no effect on the IDO activity itself but did have a synergistic effect on the IDO-induced bacteriostasis in MDM cultures. We conclude that therapy with indomethacin may increase the risk of clinically important bacterial infection due to the inhibition of the IDO-induced bacteriostasis. In addition sub-inhibitory concentrations of ampicillin may play a role in the area of infection where IFNgamma stimulated macrophages are to be found in abundance.
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PMID:Regulation of IDO-mediated bacteriostasis in macrophages: role of antibiotics and anti-inflammatory agents. 1520 17

The development of a nosocomial pneumonia is facilitated by alterations in host innate pulmonary antibacterial defenses following surgical trauma, which can result in decreased pulmonary bacterial clearance and increased morbidity and mortality. In a murine model of postoperative nosocomial infection, surgical stress (laparotomy) decreased Escherichia coli clearance from the lungs of animals that underwent surgery. Consistent with previous studies, (i) pulmonary levels of tumor necrosis factor alpha at 6 h and of interleukin-1beta (IL-1beta), IL-6, and gamma interferon (IFN-gamma) at 24 h post-bacterial infection (PBI) were decreased in animals that underwent laparotomy 24 h prior to E. coli infection (LAP/E. coli) compared to animals that received E. coli only; (ii) KC and macrophage inhibitory protein 2 were elevated at 6 h PBI in LAP/E. coli animals compared to E. coli-only animals; however, at 24 h PBI, levels were higher in the E. coli-only group; (iii) at 24 h PBI, monocyte chemoattractant protein 1 was lower in the LAP/E. coli group compared to the E. coli-only group; (iv) IL-10 levels were unaffected at all time points evaluated; and (v) the total number of neutrophils present in the lungs of LAP/E. coli animals at 6 h PBI was decreased in comparison to that in E. coli-only animals, resulting in decreased bacterial clearance and increased mortality in LAP/E. coli animals by 24 h PBI. Similar changes in cytokine profiles, pulmonary bacterial clearance, and mortality were consistent with reported findings in patients following surgical trauma. This model, therefore, provides a clinically relevant system in which the molecular and cellular mechanisms that lead to the development of nosocomial pneumonia can be further explored.
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PMID:Bacterial clearance and cytokine profiles in a murine model of postsurgical nosocomial pneumonia. 1524 50

The purpose of this study was to investigate whether, in a stable social environment, social interactions are responsible for individual, endocrine and immune differences among group members. Cage-mates were classified according to their rank in a food competition test. The influence of the rank was evaluated in two different situations activating neuroendocrine and immune systems. A first experiment used a context of repeated social stress. A second experiment investigated the influence of rank on the response to a bacterial infection by BCG. Endocrine and immune functions were assessed by measuring plasma corticosterone levels, splenocyte proliferation and in vitro cytokine production. In control undisturbed groups, plasma levels of corticosterone were lower in low ranking (LR) mice than in intermediate (IR) and high ranking (HR) mice. LPS-induced splenocyte proliferation and in vitro cytokine production were independent of rank. In response to social stress, corticosterone increased similarly in all categories but the increase in splenocyte proliferation was more pronounced in HR animals. During BCG infection, the rank influenced the production of IL-10 and IFN-gamma by tuberculin-stimulated splenocytes during the acute phase of the infection but not after 94 days of infection. Cytokine production in response to LPS and bacterial growth were not affected by the rank. Therefore, social interactions emerging in a stable social group may be involved in the individual differences observed in endocrine activity and in immune system reactivity.
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PMID:The rank assessed in a food competition test influences subsequent reactivity to immune and social challenges in mice. 1526 40

Protective immunity to the intracellular bacterial pathogen, Listeria monocytogenes, is mediated by a vigorous T cell response. In particular, CD8(+) cytolytic T cells provide essential effector function in the clearance of bacterial infection. The cytoplasmic entry of Listeria facilitated by listeriolysin O is an essential feature not only of the bacteria's virulence, but of the ability of the bacteria to elicit protective immunity in the host. To determine how cytoplasmic entry of Listeria regulates the development of protective immunity, we examined the effects of this process on the maturation of murine dendritic cells (DC) and on their ability to prime naive CD8(+) T cell responses. Costimulatory molecules (CD40, CD80, and CD86) were induced by listerial infection only when the bacteria invaded the cytoplasm. In addition, the production of IL-12, IL-10, IL-6, and TNF-alpha was most efficiently triggered by cytosolic Listeria. Naive T cells primed by peptide-loaded DC infected with either wild-type or nonhemolytic mutant Listeria proliferated equivalently, but a much larger proportion of those primed by wild-type Listeria monocytogenes produced IFN-gamma. Costimulatory molecules induced by cytosolic entry regulated T cell proliferation and, as a result, the number of functional T cells generated. DC-produced cytokines (specifically IL-12 and IL-10) were the major factors determining the proportion of T cells producing IFN-gamma. These data highlight the requirement for listerial cytoplasmic invasion for the optimal priming of T cell cytokine production and attest to the importance of this event to the development of protective CTL responses to this pathogen.
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PMID:Cytoplasmic entry of Listeria monocytogenes enhances dendritic cell maturation and T cell differentiation and function. 1529 81


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