Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used a murine respiratory challenge model to examine the local T cell responses in the lung during infection with Bordetella pertussis. T cells from lung parenchyma and airways of naive and infected mice were refractory to both antigen and mitogen stimulation in the presence of lung macrophages. Furthermore irradiated mononuclear cells from the lungs suppressed antigen and mitogen-induced proliferation, but not IFN-gamma production, by splenic T cells. Removal of macrophages and stimulation of purified lung T cells in the presence of irradiated splenic antigen-presenting cells fully restored the response to mitogen. However, T cells purified from the lung during the acute phase of infection with B. pertussis failed to proliferate or produce detectable levels of IL-2, IL-4, IL-5 or IFN-gamma in response to purified bacterial antigens. In contrast, splenic T cells from these animals produced high levels of IL-2 and IFN-gamma and proliferated strongly to a range of bacterial components. Phenotypic analysis of bronchoalveolar lavage cells during the course of infection revealed transient infiltration of neutrophils, followed by macrophages, CD4+ T cells and smaller numbers of CD8+ T cells and gammadelta+ T cells. Cell surface expression of B7 on infiltrating macrophages and CTLA-4 on T cells did not change significantly during infection. However, expression of the CD28 co-stimulatory molecule was profoundly reduced on lung T cells during the acute phase of infection. In contrast, lung T cells from mice primed by B. pertussis infection or vaccination were resistant to CD28 down-regulation. These results suggest compartmentalization of T cell responses between the lung and the periphery during B. pertussis infection and that B. pertussis may have immunomodulatory properties on local T cell populations in the lungs of naive mice.
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PMID:Compartmentalization of T cell responses following respiratory infection with Bordetella pertussis: hyporesponsiveness of lung T cells is associated with modulated expression of the co-stimulatory molecule CD28. 948 95

Nitric oxide (NO) induction was studied in the peritoneal macrophages and spleen cells of female NIH mice immunised with whole cell Bordetella pertussis vaccines of moderate and high potency, respectively. Compared with controls receiving diluent only, the macrophages and spleen cells of the vaccinated mice developed high levels of reactive nitrogen intermediates from the third day after injection. The nitrite concentrations achieved maximum values at the 10th day, but significant levels persisted until the 25th day. Heat-killed B. pertussis cells were the most effective inducer of NO synthesis, followed by lipopolysaccharide and agglutinogens Fim 2 and 3. Pertussis toxoid, filamentous haemagglutinin and pertactin were poor inducers of NO synthesis. The specific nitric oxide synthase inhibitor, aminoguanidine, and anti-IFN-gamma antibody blocked formation of nitrite by the macrophages and spleen cells. The production of NO in response to in vitro culture with bacterial antigen was clearly associated with protective immunity in vivo as determined by i.c. challenge. These results suggest that reactive nitrogen intermediates play a role in the immune response induced by whole cell pertussis vaccines.
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PMID:Nitric oxide induction in murine macrophages and spleen cells by whole-cell Bordetella pertussis vaccine. 960 4

Pertussis toxin (PT) is a major virulence factor of Bordetella pertussis which exerts a range of effects on the immune system, including the enhancement of IgE, IgA and IgG production, delayed-type hypersensitivity reactions, and the induction of experimental autoimmune diseases. However, the mechanism by which PT mediates adjuvanticity remains to be defined. In this investigation we have shown that PT can potentiate antigen-specific T cell proliferation and the secretion of IFN-gamma, IL-2, IL-4 and IL-5 when injected with foreign antigens. A chemically detoxified PT and a genetic mutant with substitutions/deletions in the S-1 and B oligomer components that abrogate enzymatic and binding activity displayed no adjuvant properties. In contrast, a non-toxic S-1 mutant devoid of enzymatic activity but still capable of receptor binding retained its adjuvanticity, augmenting the activation of both Th1 and Th2 subpopulations of T cells. In an attempt to address the mechanism of T cell activation, we found that PT stimulated the production of IFN-gamma and IL-2 by naive T cells and IL-1 by macrophages. Therefore potentiation of distinct T cell subpopulations may have resulted in part from the positive influence of IFN-gamma on the development of Th1 cells and the co-stimulatory role of IL-1 for Th2 cells. Furthermore, PT augmented expression of the co-stimulatory molecules B7-1 and B7-2 on macrophages and B cells, and CD28 on T cells, suggesting that the adjuvant effect may also be associated with facilitation of the second signal required for maximal T cell activation. This study demonstrates that the immunopotentiating properties of PT are largely independent of ADP-ribosyltransferase activity, but are dependent on receptor binding activity and appear to involve enhanced activation of T cells.
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PMID:Pertussis toxin potentiates Th1 and Th2 responses to co-injected antigen: adjuvant action is associated with enhanced regulatory cytokine production and expression of the co-stimulatory molecules B7-1, B7-2 and CD28. 964 13

There is increasing evidence that the cellular immune response to Bordetella pertussis plays an important role in the immune protection. Particularly in animal models, Bordetella pertussis-specific T-cells have been shown to confer immunity. In this case report, we therefore investigated the cellular immune response to whole cell Bordetella pertussis bacteria, to the pertussis antigens filamentous hemagglutinin and pertussis toxoid defined by lymphoproliferation and cytokine secretion. Two children with whooping cough were compared to three individuals vaccinated against whooping cough with a whole cell pertussis vaccine. In contrast to the vaccinated controls, the cellular immune response to Bordetella pertussis in children with whooping cough was characterized by a strong proliferation of T cells to whole pertussis bacteria as well as to filamentous hemagglutinin and pertussis toxoid. This response was defined by a marked Th-1 type T cell response with IFN-gamma secretion to all Bordetella pertussis antigens. However, in the control individuals IFN-gamma was secreted only to whole cell Bordetella pertussis bacteria and filamentous hemagglutinin but not to pertussis toxoid. A Th-2 type cytokine response could not be detected in any condition. Our observations suggest that in the immune defense of a natural Bordetella pertussis infection, the Th-1 specific T cell response to filamentous hemagglutinin and particularly to pertussis toxoid may play a major role.
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PMID:The cellular immune response to Bordetella pertussis in two children with whooping cough. 981 32

The aim of the present study was to examine the in vivo effect of interleukin (IL)-12 on a murine model of asthma induced by Dermatophagoides pteronyssinus-derived Der p 1 allergen. C57BL/6 mice immunized with Der p 1 allergen adsorbed to alum/pertussis toxin developed a T-helper type 2 (Th2)-dominant immune response characterized by the presence of IgE antibody, airway eosinophil infiltration and increased production of Th2 cytokine. Intraperitoneal injection of IL-12 (1 or 0.1 microg per day) for 5 days (day -1 to +3) simultaneously with each immunization, inhibited the production of IgE and IgG1 antigen-specific antibodies, whereas production of IgG2a was strongly enhanced. In addition, mice receiving both doses of IL-12 showed a strong inhibition of IL-5 but up-regulation of IFN-gamma production by spleen cells stimulated with antigen. Administration of IL-12 also prevented antigen-induced eosinophil infiltration into the bronchoalveolar area in a dose-dependent manner and the primary inflammatory mediator serotonin in bronchoalveolar lavage (BAL) fluids was also reduced significantly. Taken together, the data indicate that IL-12 has a potent immunomodulatory effect on house-dust-mite-induced allergic disorders and may be used as an efficient agent for immunotherapy.
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PMID:Administration of interleukin-12 prevents mite Der p 1 allergen-IgE antibody production and airway eosinophil infiltration in an animal model of airway inflammation. 1010 39

The role of IFN-gamma in reducing the intracellular load of Bordetella pertussis in murine macrophages in vitro has been examined. The results demonstrate that exposure to IFN-gamma can reduce bacterial load in viable macrophages and that this is associated with production of nitric oxide (NO). These observations provide a mechanism by which IFN-gamma may mediate its antimicrobial effect and support an important role for activated alveolar macrophages in the elimination of B. pertussis from the respiratory tract. Using intracellular iron chelation, it is shown that intracellular survival of B. pertussis is dependent on iron availability and suggest that iron restriction may be an important mechanism by which IFN-gamma influences bacterial survival within mouse macrophages. It is also shown that IFN-gamma may mediate its effect through NO independent mechanisms and that B. pertussis is sensitive to agents that stimulate the respiratory burst. Finally, it is shown that the concentration of L-tryptophan may be a limiting step in the intracellular survival of B. pertussis and that the induction of tryptophan degrading enzymes may be an additional mechanism through which IFN-gamma exerts its antimicrobial effects against B. pertussis.
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PMID:Interferon-gamma mediated immune effector mechanisms against Bordetella pertussis. 1042 23

The systemic transfer of ex vivo-activated tumor-sensitized T lymphocytes can mediate immunologically specific regression of established tumors. However, it has not been conclusively established whether the infiltration of systemically transferred T cells into metastases is required for their effector function. In this study, T cells from lymph nodes draining the murine fibrosarcoma MCA 205 cells were activated ex vivo with anti-CD3 monoclonal antibody and interleukin-2. During the final 24 h of culture, the T cells were treated with pertussis toxin (PTX) to inhibit signaling through G protein-coupled chemokine receptors required for diapedesis. Systemically transferred PTX-treated cells did not have any therapeutic efficacy against 3-day established pulmonary metastases. This lack of efficacy correlated with their failure to infiltrate the tumor parenchyma. However, PTX-treated cells responded to tumor antigen stimulation with IFN-gamma secretion in vitro. More importantly, PTX-treated effector T cells prevented tumor growth when they were admixed with tumor cells and inoculated s.c. These results demonstrate that systemically transferred tumor-reactive T lymphocytes need to infiltrate the tumor parenchyma through the endothelium to initiate tumor regression, but PTX-sensitive proteins are not required for either antigen recognition or effector functions.
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PMID:Infiltration of tumors by systemically transferred tumor-reactive T lymphocytes is required for antitumor efficacy. 1053 4

IL-12 plays a critical role in protective immunity against intracellular pathogens by promoting the development of Th1 cells. Here we demonstrate that filamentous hemagglutinin (FHA), a virulence factor of Bordetella pertussis, is capable of suppressing IL-12 production by macrophages. FHA inhibited IL-12 secretion by a macrophage cell line or ex vivo alveolar macrophages in response to Escherichia coli or B. pertussis lipopolysaccharide (LPS) and IFN-gamma. Antibodies to FHA or denaturation of FHA abrogated the inhibitory effect. Injection of mice with FHA suppressed IL-12 and IFN-gamma levels in the serum in response to i. v. injection of LPS in a model of septic shock. The suppressive effect of FHA was specific for IL-12, since the production of TNF-alpha, IL-6 and IL-10 was not suppressed, and production of IL-6 and IL-10 was up-regulated. Antibody blocking studies revealed that the inhibitory effect of FHA on IL-12 production was dependent on IL-10. Since FHA is secreted at high levels and local T cell responses are suppressed during B. pertussis infection, the findings suggest that FHA may be a critical virulence factor in facilitating pathogen persistence in the respiratory tract by suppressing or delaying the development of cell-mediated immunity.
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PMID:Direct anti-inflammatory effect of a bacterial virulence factor: IL-10-dependent suppression of IL-12 production by filamentous hemagglutinin from Bordetella pertussis. 1067 Nov 96

To elucidate the factor(s) accelerating the autoimmune disease processes, we induced two types of experimental autoimmune encephalomyelitis (EAE), severe and very mild, in F344 rats by immunization with myelin basic protein (MBP) plus pertussis toxin (PT) (PT+) or with MBP alone (PT-) and compared the differences between the two. Immunohistochemical examinations showed that although the nature of inflammation was essentially the same between the two groups, the proportion of Vbeta8.2(+) T cells in the CNS lesion of PT (+) rats was larger than that of PT (-) rats. Cytokine analysis by competitive PCR revealed that IL-10 mRNA in the lymphoid organ was significantly suppressed in the PT(+) group, whereas levels of IFN-gamma,TNF-alpha and TGF-beta mRNA were insignificantly different after PT administration. In addition, T cells taken from PT (+) rats proliferated well in response to MBP, while those from PT (-) rats showed a marginal response to the same antigen. However, this finding does not indicate the switching of non-encephalitogenic to encephalitogenic T cells upon PT administration because PT (-) rats contained encephalitogenic T cells and/or their precursor cells as revealed by adoptive transfer experiments. Taken together, these findings suggest that suppression of IL-10 by PT administration is the major factor contributing to the exacerbation of EAE in PT(+) rats.
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PMID:Analysis of experimental autoimmune encephalomyelitis induced in F344 rats by pertussis toxin administration. 1068 10

In this study, mouse recombinant IFN-beta was shown to favor PLP139-151-specific Th2 responses in vitro, by inhibiting IFN-gamma production and stimulating IL-4 and IL-10 production. IFN-beta (5000 U/day) failed to prevent the development or severity of EAE induced with PLP139-151. Whereas efficacy of IL-10 was found in the B. pertussis assisted but not in the pertussigen-assisted EAE model, both models appeared insensitive to IFN-beta. Also the combination of (suboptimal) IL-10 and IFN-beta appeared ineffective in inhibiting disease. However, the PLP139-151-specific IL-10 production by T cells from these mice appeared significantly more sensitive to the stimulatory effect of IFN-beta in vitro. It is concluded that despite its Th2 promoting effects, IFN-beta is not effective in inhibiting EAE in this study.
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PMID:IFN-beta modulates specific T cell responses in vitro but does not affect Experimental Autoimmune Encephalomyelitis in the SJL mouse. 1069 29


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