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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a murine respiratory challenge model we have previously demonstrated a role for Th1 cells in natural immunity against Bordetella pertussis, but could not rule out a role for antibody. Here we have demonstrated that B. pertussis respiratory infection of mice with targeted disruptions of the genes for the IFN-gamma receptor resulted in an atypical disseminated disease which was lethal in a proportion of animals, and was characterized by pyogranulomatous inflammation and postnecrotic scarring in the livers, mesenteric lymph nodes and kidneys. Viable virulent bacteria were detected in the blood and livers of diseased animals. An examination of the course of infection in the lung of IFN-gamma receptor-deficient, IL-4-deficient and wild-type mice demonstrated that lack of functional IFN-gamma or IL-4, cytokines that are considered to play major roles in regulating the development of Th1 and Th2 cells, respectively, did not affect the kinetics of bacterial elimination from the lung. In contrast, B cell-deficient mice developed a persistent infection and failed to clear the bacteria after aerosol inoculation. These findings demonstrate an absolute requirement for B cells or their products in the resolution of a primary infection with B. pertussis, but also define a critical role for IFN-gamma in containing bacteria to the mucosal site of infection.
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PMID:Atypical disease after Bordetella pertussis respiratory infection of mice with targeted disruptions of interferon-gamma receptor or immunoglobulin mu chain genes. 938 83

Using a mouse model of Bordetella pertussis infection, we have analyzed the role of gamma interferon (IFN-gamma) in bacterial clearance from the respiratory tract. Adult BALB/c mice began to clear a respiratory infection within 3 weeks postinfection, with complete resolution of infection 6 to 8 weeks postinfection. In contrast, neither adult SCID mice (which lack mature B and T lymphocytes) nor adult nude mice (which lack mature T lymphocytes) controlled B. pertussis infection, and both strains died within 3 to 5 weeks postinfection. Short-term T-cell lines generated from the draining lymph nodes of the lungs of infected BALB/c mice were found to be CD4+ and produced IFN-gamma but no detectable interleukin-4. Analyses of IFN-gamma mRNA induction in the lungs of mice following B. pertussis infection showed that in both BALB/c and C57BL/6 mice, IFN-gamma mRNA levels increased sharply by 1 week postinfection and then subsequently declined. Further exploration of a potential role for IFN-gamma demonstrated that infection of adult BALB/c mice depleted of IFN-gamma in vivo with anti-IFN-gamma monoclonal antibodies resulted in greater numbers of bacteria recovered from the lungs than in infected, control BALB/c mice, although IFN-gamma-depleted mice could subsequently clear the infection. Infection of mice which have a disrupted IFN-gamma gene resulted in bacterial clearance with a time course similar to those seen with IFN-gamma-depleted mice. These results indicate that IFN-gamma plays a role in controlling B. pertussis infection.
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PMID:Role of gamma interferon in natural clearance of Bordetella pertussis infection. 939 74

The results of phase 3 efficacy trials have shown that acellular and whole-cell pertussis vaccines can confer protection against whooping cough. However, despite the advances in vaccine development, clinical trials have not provided significant new information on the mechanism of protective immunity against Bordetella pertussis. Classical approaches based on measurement of antibody responses to individual antigens failed to define an immunological correlate of protection. A reliable animal model, predictive of acellular and whole-cell pertussis vaccine potency in children, would facilitate an elucidation of the mechanism of immune protection against B. pertussis and would assist in the regulatory control and future development of pertussis vaccines. In this study, we have shown that the rate of B. pertussis clearance following respiratory challenge of immunized mice correlated with vaccine efficacy in children. Using this model together with mice with targeted disruptions of the gamma interferon (IFN-gamma) receptor, interleukin-4 or immunoglobulin heavy-chain genes, we have demonstrated an absolute requirement for B cells or their products in bacterial clearance and a role for IFN-gamma in immunity generated by previous infection or immunization with the whole-cell pertussis vaccine. The results of passive immunization experiments suggested that protection early after immunization with acellular pertussis vaccines is mediated by antibody against multiple protective antigens. In contrast, more complete protection conferred by previous infection or immunization with whole-cell pertussis vaccines reflected the induction of Th1 cells. Our findings suggest that the mechanism of immunity against B. pertussis involves humoral and cellular immune responses which are not directed against a single protective antigen and thus provide an explanation for previous failures to define an immunological correlate of protection.
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PMID:A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis. 945 14

The effect on antigen (Ag)-specific Th2 response as well as IgE production of continuous oral administration of micro-doses of Ag was investigated. Transgenic (Tg) mice carrying the alphabeta-T cell receptor (TCR) genes specific for ovalbumin (OVA) peptide fragment 323-339 were continuously fed with micro-doses of OVA (100 microg/day) for 14 days. Mice were first immunized by OVA in alum and pertussis toxin 7 days before the oral feeding and given a second immunization 1 day after the oral treatment. This feeding regimen tolerized Th2 but not Th1 responses as shown by decrease of Ag-driven cell proliferation and cytokine secretion of IL-4 but not of IL-2 or IFN-gamma as well as by the absence of Ag-specific antibody production of IgE and IgG1, but not of IgG2a or total IgG. Numbers of clonotype-specific TCR-high CD4-positive T cells in peripheral lymphoid tissues markedly decreased in the orally treated group but not in the control group. However, total numbers of CD4-positive T cells in thymus, spleen and lymph nodes were not affected by the oral treatment, indicating that tolerance induction in Th2 cells was mainly due to the down-regulation of TCR and not clonal deletion. The population of antigen-presenting cells expressing B7-2 (CD86) Ag on the surface was decreased in the spleen of the mice which underwent the feeding regimen. The present results suggest that Ag-specific low responsiveness in Th2 cells, which resulted in suppression of the Ag-specific IgE production, can be achieved by continuous feeding with microdoses of Ag.
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PMID:Selective suppression of antigen-specific Th2 cells by continuous micro-dose oral tolerance. 948 93

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

Pertussis infection is increasingly recognized in older children and adults, indicating the need of booster immunizations in these age groups. We investigated the induction of pertussis-specific immunity in schoolchildren and adults after booster immunization and natural infection. The expression of mRNA of gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-5 in the peripheral blood mononuclear cells (PBMCs) was assayed by reverse transcription-PCR. The PBMCs of 17 children immunized with one dose of an acellular vaccine containing pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) significantly proliferated in vitro after stimulation with the vaccine antigens. The PBMCs of seven infected individuals markedly proliferated in the presence of PT and FHA, but the cells of only two of these subjects responded to PRN. At least one of the antigens induced mRNA for IL-4 and/or IL-5 in the cells of 93% of tested vaccinees and patients, and FHA induced IFN-gamma mRNA in the cells of two-thirds of them. Expression of mRNA for IFN-gamma correlated with the production of the cytokine protein. Anti-FHA immunoglobulin G antibodies significantly correlated with FHA-induced proliferative responses both before and after immunization. These results show that booster immunization with acellular pertussis vaccine induces both antibody- and cell-mediated immune responses in schoolchildren. Further, booster immunization and natural infection seem to induce the expression of mRNA of T-helper 1 (Th1) and Th2 type cytokines in similar manners. This observation supports the use of acellular pertussis vaccines for booster immunizations of older children, adolescents, and adults.
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PMID:Cytokine mRNA expression and proliferative responses induced by pertussis toxin, filamentous hemagglutinin, and pertactin of Bordetella pertussis in the peripheral blood mononuclear cells of infected and immunized schoolchildren and adults. 967 64

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


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