RESUMO
Activation of macrophages plays an important role in the host resistance against intracellular pathogens. Various mechanisms are employed to control the activation processes and limit tissue damage by factors produced by activated macrophages. One of these mechanisms is the production of macrophage-deactivating cytokines, such as tumour growth factor (TGF)-beta. The present study concerns the effects of TGF-beta on interferon (IFN)-gamma-induced activation of murine macrophages with respect to induction of toxoplasmastatic activity, and production of tumour necrosis factor (TNF)-alpha, prostaglandin E2 (PGE2) and reactive nitrogen intermediates (RNI). IFN-gamma activation of macrophages resulted in inhibition of T. gondii proliferation [mean fold increase (FI) = 1.8, control mean FI = 7.0]; polymyxin B had no effect on this activation. The IFN-gamma-induced toxoplasmastatic activity of macrophages was inhibited by TGF-beta (mean FI = 6.3), which was also found for the IFN-gamma-induced production of TNF-alpha, RNI and PGE2 by macrophages. We found that PGE2, which has macrophage deactivating properties, was not involved in the inhibition of macrophage activation by TGF-beta. The deactivating activities of TGF-beta on the IFN-gamma-induced toxoplasmastatic activity and production of RNI are mediated by inhibition of production of TNF-alpha. Addition of exogenous TNF-alpha during the incubation of macrophages with IFN-gamma and TGF-beta abrogated the deactivating activity of TGF-beta. In sum, the results demonstrate that inhibition of TNF-alpha production is a key factor in the TGF-beta-induced suppression of macrophage activation with respect to toxoplasmastatic activity and RNI production.
Assuntos
Interferon gama/antagonistas & inibidores , Linfotoxina-alfa/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/parasitologia , Fatores Supressores Imunológicos/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Dinoprostona/análise , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Endogâmicos CBA , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/metabolismo , Organismos Livres de Patógenos Específicos , Toxoplasma/efeitos dos fármacos , Toxoplasma/crescimento & desenvolvimento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The antibody production by HIV-infected adults after two vaccinations with conjugated pneumococcal vaccine (CPV) and consecutive vaccination with polysaccharide pneumococcal vaccine (PPV) was studied. Thirty days after the second CPV, the geometric mean antibody concentrations (GMC) against pneumococcal polysaccharide serotypes (PPS) 6B, 14 and 19F were significantly lower in the group HIV-infected individuals with <200x10(6)/l CD4(+) T lymphocytes (group 1) than in the group with >/=200x10(6)/l CD4(+) T lymphocytes (group 2) and healthy controls. Thirty days after PPV vaccination the GMC against PPS 6B, 14, 19F and 23F in group 1, and against 6B and 19F in group 2, were significantly lower compared with healthy controls. Both in HIV-infected and in healthy individuals who received CPV and PPV the postvaccination GMC against PPS 14, 19F and 23F were higher compared with historical controls who were not previously immunized with CPV but only received PPV. We conclude that the antibody response to CPV is impaired in HIV-infected individuals. Higher antibody concentrations were achieved in HIV-infected and healthy individuals after sequential vaccination with CPV and PPV compared with PPV vaccination alone.
Assuntos
Anticorpos Antibacterianos/biossíntese , Infecções por HIV/imunologia , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Adulto , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/efeitos adversos , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologiaRESUMO
The aim of this study was to investigate the effect of interleukin-10 (IL-10) on the course of Listeria monocytogenes infection in naive and immune mice. Treatment with IL-10 during the course of a primary infection significantly decreased the number of bacteria in the spleen and did not affect the number in the liver. During a secondary infection in immune mice treated with IL-10, the number of bacteria was significantly lower in the spleen but significantly higher in the liver in comparison to mock-treated immune mice. IL-10 treatment during a primary Listeria infection decreased the concentration of gamma interferon (IFN-gamma) in plasma and the toxoplasmastatic activity of macrophages, whereas it increased the percentage of mildly CD3-positive T cells in the spleen. During a secondary infection, the concentration of IFN-gamma in plasma was decreased on day 1 but remained unaffected during later days of infection. From these results, we conclude that IL-10 has different effects on the proliferation of L. monocytogenes in the spleen and liver during primary and secondary Listeria infections.
Assuntos
Interleucina-10/imunologia , Listeriose/imunologia , Fígado/microbiologia , Baço/microbiologia , Animais , Anticorpos Monoclonais/farmacologia , Complexo CD3/análise , Divisão Celular/efeitos dos fármacos , Feminino , Interferon gama/sangue , Interleucina-10/uso terapêutico , Listeriose/tratamento farmacológico , Fígado/citologia , Ativação de Macrófagos , Camundongos , Camundongos Endogâmicos CBA , Receptores de Antígenos de Linfócitos T alfa-beta , Baço/citologia , Subpopulações de Linfócitos T , Células Th1RESUMO
In 1996 an unexpected rise in the incidence of whooping cough occurred in the Netherlands, and antigenic divergence between vaccine strains and clinical isolates has been suggested as a cause for this phenomenon. To investigate this assumption, the binding of murine antibodies against the whole-cell pertussis vaccine or filamentous haemagglutinin, an important protective antigen, to a limited number of Bordetella pertussis strains isolated during different time-periods (1991-92, 1994 and 1996) was assessed. The results showed that all strains were recognized equally well by these antisera, indicating that filamentous haemagglutinin was unchanged during the time-periods examined. Although over the years changes have occurred in at least two surface proteins of B. pertussis, these changes are too subtle to be recognized by the antibodies raised in mice. Further research is required to assess whether antigenic variation of B. pertussis has an effect on protective immunity.
Assuntos
Adesinas Bacterianas/imunologia , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Bordetella pertussis/imunologia , Hemaglutininas/imunologia , Vacina contra Coqueluche/imunologia , Fatores de Virulência de Bordetella , Animais , Anticorpos Antibacterianos/sangue , Pré-Escolar , Humanos , Lactente , Camundongos , Camundongos Endogâmicos BALB C , Países Baixos/epidemiologia , Coqueluche/epidemiologia , Coqueluche/imunologia , Coqueluche/microbiologiaRESUMO
In a consecutive 3-year study the antibody response after immunization with influenza vaccine of a cohort of HIV-infected adults was studied. The haemagglutination-inhibiting (HAI) antibody titres after vaccination correlated with the number of CD4(+) T lymphocytes (p<0.001), the prevaccination antibody titres (p<0.001), and the proliferative response to anti-CD3 (p<0.001). Severely impaired antibody responses were observed in HIV-infected individuals with CD4(+) T-lymphocyte counts < or =100x10(6)/l. Significantly higher prevaccination antibody titres were observed in healthy controls in the 2nd or 3rd year of vaccination, but not in HIV-infected individuals. Annually repeated vaccination of HIV-infected individuals did not lead to higher postvaccination antibody titres. Annual vaccination of HIV-infected individuals with CD4(+) T-lymphocyte counts exceeding 100x10(6)/l seems to be worthwhile, although it may not be expected to render the same level of protection against influenza as in non-infected individuals.
Assuntos
Anticorpos Antivirais/sangue , Infecções por HIV/imunologia , Vacinas contra Influenza/imunologia , Adulto , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Humanos , Estudos Prospectivos , Fatores de Tempo , VacinaçãoRESUMO
In the present study, protection against Bordetella pertussis infection and humoral immunological responses in mice has been assessed upon immunization with custom-made acellular pertussis vaccines (ACVs) and whole-cell pertussis vaccine (WCV). Mice were immunized, next intranasally infected with B. pertussis and during 14 days the number of bacteria in the trachea and lungs and the level of serum antibodies were determined. ACV contained five immunogens, filamentous hemagglutinin, pertactin, fimbriae serotypes 2 and 3, and chemically detoxified pertussis toxin (PMC-5), or three immunogens, filamentous hemagglutinin, pertactin, and genetically detoxified (BC-3) or chemically detoxified pertussis toxin (SKB-3). Immunization with a high or low dose of ACV or WCV resulted in significant protection against B. pertussis, with differences in the degree of protection between the vaccines. The lowest protection was found with a low dose of SKB-3 and WCV. The pattern of cytokine production by spleen cells of immunized, non-infected, mice indicated that T-helper 1 cells are activated by vaccination with WCV, and T-helper 1 and T-helper 2 cells are involved in the immune response upon vaccination with ACVs. Each vaccine stimulated the production of IgG, but not IgA, antibodies. In mice immunized with ACV, elimination of B. pertussis from trachea and lungs correlated significantly with the titre of IgG1, but not IgG2a, antibodies.
Assuntos
Anticorpos Antibacterianos/biossíntese , Bordetella pertussis/imunologia , Vacina contra Coqueluche/imunologia , Coqueluche/prevenção & controle , Animais , Citocinas/biossíntese , Imunização , Imunoglobulina G/biossíntese , Imunoglobulina G/classificação , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Traqueia/microbiologia , Vacinas Acelulares/imunologiaRESUMO
Bordetella pertussis interacts with very-late antigen-5 (VLA-5) receptors on the human monocyte resulting in cross-linking of these receptors followed by activation of complement receptor 3 (CR3) and firm adhesion of B. pertussis to these monocytes. In the present study we investigated whether protein tyrosine kinases are involved in the activation of CR3 on monocytes, which was assessed by the binding of C3bi-coated erythrocytes (EC3bi). Pre-incubation of monocytes with tyrphostin-A47, a specific protein tyrosine kinase inhibitor, before adherence of the cells to an anti-VLA-5 monoclonal antibody-coated surface, or addition of tyrphostin-A47 within 10 min of the adherence to such surface, reduced the binding of EC3bi to monocytes significantly. Pre-incubation of monocytes with tyrphostin-A47 reduced the binding of B. pertussis to such monocytes as well. Inhibitors of protein kinase A and/or C had no effect on EC3bi binding to monocytes. Cross-linking of VLA-5 on monocytes resulted in tyrosine phosphorylation of several proteins. Together, these results indicate that protein tyrosine kinases are involved in the VLA-5-induced activation of CR3 on human monocytes.
Assuntos
Bordetella pertussis/imunologia , Ativação do Complemento/imunologia , Eritrócitos/imunologia , Antígeno de Macrófago 1/imunologia , Proteínas Tirosina Quinases/metabolismo , Receptores de Fibronectina/imunologia , Anticorpos Monoclonais , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Fosforilação , Inibidores de Proteínas Quinases , Proteínas Tirosina Quinases/antagonistas & inibidores , Estaurosporina/farmacologia , Tirfostinas/farmacologiaRESUMO
We studied the production of IgG antibodies against eight pneumococcal polysaccharide serotypes (PPS) 1, 4, 6B, 9V, 14, 18C, 19F and 23F after vaccination of 50 HIV-infected adults with 23-valent Pneumovax((R))23 and the course of the antibodies against four PPS during the following years. Mean antibody concentrations against PPS 18C, 19F and 23F were sigificantly lower in the patients with CD4(+)-lymphocyte counts <200x10(6)/l than in healthy controls; mean antibody concentrations against PPS 1, 4, 9V, 6B and 14 were similar in HIV-infected individuals and controls. Although it has been assumed that polysaccharides induce a T-cell-independent immune response, our results indicate that some PPS are T-cell-independent type 2 antigens. The rates of decline of mean antibody concentrations in HIV-infected individuals and in healthy controls were similar during 5 y after vaccination. However, as a consequence of the low postvaccination antibody concentrations against several PPS, within 3 y after vaccination most HIV-infected individuals had antibody concentrations below the level which is assumed to be required for protection.
Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/imunologia , Infecções por HIV/imunologia , Streptococcus pneumoniae/imunologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas , Linfócitos T/imunologia , Fatores de Tempo , VacinaçãoRESUMO
Previously we have identified and characterized three murine microbicidal proteins purified from the granule fraction of cells from the murine macrophage cell line RAW264.7. During these studies evidence was obtained for the presence of an additional antimicrobial protein in the cytosolic fraction of RAW264.7 cells that had been activated with interferon-gamma (IFN-gamma). In this study we have purified this protein, designated ubiquicidin, to apparent homogeneity and demonstrated that it is a cationic, small (Mr 6654) protein. Ubiquicidin displayed marked antimicrobial activity against Listeria monocytogenes and Salmonella typhimurium. Using a gel overlay procedure evidence was obtained that the protein also displays activity against Escherichia coli, Staphylococcus aureus, and an avirulent strain of Yersinia enterocolitica. Aminoterminal amino acid sequencing and mass spectrometry analysis of purified ubiquicidin indicated that it is most likely identical to the ribosomal protein S30. This protein is produced by posttranslational processing of the Fau protein, a 133-amino-acid fusion protein consisting of S30 linked to an unusual peptide with significant homology to ubiquitin. The fau gene has been reported to be expressed in a variety of tissues in humans and various animal species. The presence of ubiquicidin in the cytosol of macrophages may serve to restrict the intracellular growth of microorganisms. In addition, because macrophage disintegration will likely lead to release of ubiquicidin into the extracellular environment, it may contribute to host defense after macrophage death.
Assuntos
Bactérias/efeitos dos fármacos , Macrófagos/química , Sequência de Aminoácidos , Animais , Citosol/química , Defensinas , Escherichia coli/efeitos dos fármacos , Interferon gama/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Espectrometria de Massas , Camundongos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Peso Molecular , Proteínas de Neoplasias/isolamento & purificação , Proteínas de Neoplasias/metabolismo , Proteínas/farmacologia , Coelhos , Ratos , Proteínas Ribossômicas/química , Proteínas Ribossômicas/metabolismo , Salmonella typhimurium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Células Tumorais Cultivadas , Yersinia enterocolitica/efeitos dos fármacosRESUMO
In the present study, the effect of treatment with granulocyte colony-stimulating factor (G-CSF) on cellular composition of the bone marrow and the number of circulating leucocytes of granulocytopenic mice, whether or not infected with Staphylococcus aureus, was assessed. With two monoclonal antibodies, six morphologically distinct cell populations in the bone marrow could be characterised and quantitated by two-dimensional flow cytometry. Granulocytopenia was induced by cyclophosphamide or sublethal irradiation. Cyclophosphamide predominantly affected the later stages of dividing cells in the bone marrow resulting in a decrease in number of granulocytic cells, monocytic cells, lymphoid cells and myeloid blasts. G-CSF administration to cyclophosphamide-treated mice increased the number of early blasts, myeloid blasts and granulocytic cells in the bone marrow, which indicates that this growth factor stimulates the proliferation of these cells in the bone marrow. During infection in cyclophosphamide-treated mice the number of myeloid blasts increased. However, when an infection was induced in cyclophosphamide and G-CSF-treated mice, the proliferation of bone-marrow cells was not changed compared to that in noninfected similarly treated mice. Sublethal irradiation affected all bone-marrow cell populations, including the early blasts. G-CSF-treatment of irradiated mice increased only the number of myeloid blasts slightly, whereas an infection in irradiated mice, whether or not treated with G-CSF, did not affect the number of bone-marrow cells. Together, these studies demonstrated that irradiation affects the early blasts and myeloid blasts in the bone marrow more severely than treatment with cyclophosphamide. Irradiation probably depletes the bone marrow from G-CSF-responsive cells, while cyclophosphamide spared G-CSF responsive cells, thus enabling the enhanced G-CSF-mediated recovery after cyclophosphamide treatment. Only in these mice, bone marrow recovery is followed by a strong mobilisation of mature granulocytes and their band forms from the bone marrow into the circulation during a bacterial infection.
Assuntos
Agranulocitose/terapia , Células da Medula Óssea/patologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Infecções Oportunistas/patologia , Agranulocitose/induzido quimicamente , Agranulocitose/etiologia , Animais , Antineoplásicos Alquilantes/toxicidade , Contagem de Células , Técnicas de Cultura de Células , Divisão Celular/efeitos dos fármacos , Ciclofosfamida/toxicidade , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Lesões Experimentais por Radiação/patologia , Infecções Estafilocócicas/patologia , Irradiação Corporal Total/efeitos adversosRESUMO
Infections with Salmonella species, including Salmonella typhi, are more frequently observed in HIV-infected individuals than in healthy individuals. HIV-infected individuals were vaccinated with polysaccharide vaccine against Salmonella typhi (Typhim-Vi) which is assumed to be a T-cell-independent antigen. We found that the antibody response in patients with < 200 x 10(6)/l CD4+ T lymphocytes was significantly lower compared with patients with > or = 200 x 10(6)/l CD4+ T lymphocytes and healthy controls. The antibody response after vaccination with the polysaccharide salmonella Vi-antigen was correlated with the number of CD4+ T lymphocytes and therefore Typhim-Vi can be considered to be a T-cell-independent type 2 antigen. The results of this study indicate that after vaccination the proportion of HIV-infected individuals with protective antibody concentrations against Salmonella typhi will be lower than in healthy controls.
Assuntos
Anticorpos Antibacterianos/biossíntese , Infecções por HIV/imunologia , Polissacarídeos Bacterianos/imunologia , Salmonella typhi/imunologia , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/imunologia , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Feminino , HIV-1/genética , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Polissacarídeos Bacterianos/efeitos adversos , RNA Viral/metabolismo , Vacinas Tíficas-Paratíficas/efeitos adversosRESUMO
In previous studies, we have shown that intact, heat-killed, gram-negative bacteria (GNB) and gram-positive bacteria (GPB) can stimulate the production of various proinflammatory and anti-inflammatory cytokines. The objective of the present study was to investigate whether the production of tumor necrosis factor alpha (TNF) and interleukin-10 (IL-10) by human monocytes stimulated by intact heat-killed or live Haemophilus influenzae or Streptococcus pneumoniae is mediated by CD14. Two anti-CD14 monoclonal antibodies (MAbs) were used to study the interaction between human monocytes and bacteria; lipopolysaccharide (LPS) was used to validate the effect of anti-CD14 MAb. MAb 18E12 decreased significantly TNF and IL-10 production upon stimulation with LPS or heat-killed bacteria and TNF production during stimulation by live bacteria. MAb My-4 decreased production of TNF and IL-10 by monocytes stimulated with LPS, IL-10 but not TNF production upon stimulation with heat-killed H. influenzae, and production of neither TNF nor IL-10 upon stimulation with S. pneumoniae. Together, these results led to the conclusion that CD14 is involved in the recognition and stimulation of human monocytes by intact GNB and GPB. Consequentially, the option for adjunctive treatment of severe infections with anti-CD14 MAb is postulated.
Assuntos
Anticorpos Monoclonais/farmacologia , Haemophilus influenzae/fisiologia , Interleucina-10/antagonistas & inibidores , Receptores de Lipopolissacarídeos/fisiologia , Monócitos/metabolismo , Streptococcus pneumoniae/fisiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Humanos , Receptores de Lipopolissacarídeos/imunologia , Lipopolissacarídeos/farmacologiaRESUMO
Since arachidonic acid (AA) production by phospholipase A2 (PLA2) is essential for the Fcgamma receptor (FcgammaR)-mediated respiratory burst and phagocytosis of opsonized erythrocytes by monocytes and macrophages, we focused in this study on the role of AA and its metabolites in the FcgammaR-stimulated intracellular killing of Staphylococcus aureus by human monocytes. The results revealed that the PLA2 inhibitors, but not inhibitors of cyclo-oxygenase and lipoxygenase, markedly suppressed the FcgammaR-mediated killing process. The production of O-2 by monocytes upon FcgammaR cross-linking was inhibited by 4-bromophenacyl bromide in a dose-dependent fashion, indicating that inhibition of PLA2 activity impairs the oxygen-dependent bactericidal mechanisms of monocytes, which could be partially restored by addition of exogenous AA and docosahexaenoic acid, but not myristic acid. These polyunsaturated fatty acids, but not myristic acid, stimulated the intracellular killing of S. aureus by monocytes, although not as effectively as FcgammaR cross-linking. Furthermore, FcgammaR cross-linking stimulated the release of AA from monocytes. Studies with selective inhibitors revealed that the FcgammaR-mediated activation of PLA2 is dependent on Ca2+ and tyrosine kinase activity. Together these results indicate a key role for PLA2/AA, but not its major metabolites, in mediating the FcgammaR-stimulated intracellular killing of S. aureus by monocytes.
Assuntos
Ácido Araquidônico/metabolismo , Imunoglobulina G/metabolismo , Monócitos/fisiologia , Fagocitose/efeitos dos fármacos , Receptores de IgG/metabolismo , Staphylococcus aureus , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , 4,5-Di-Hidro-1-(3-(Trifluormetil)Fenil)-1H-Pirazol-3-Amina/farmacologia , Acetofenonas/farmacologia , Ácido Araquidônico/farmacologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Inibidores de Ciclo-Oxigenase/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Genisteína/farmacologia , Humanos , Imunoglobulina G/farmacologia , Indometacina/farmacologia , Inibidores de Lipoxigenase/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Oxigênio/metabolismo , Fosfolipases A/antagonistas & inibidores , Fosfolipases A/metabolismo , Fosfolipases A2 , Proteína Quinase C/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Sulfonamidas/farmacologiaRESUMO
In human immunodeficiency virus (HIV)-infected individuals the amount of antibodies formed after vaccination with T-cell-dependent recall antigens such as tetanus toxoid is proportional to the peripheral blood CD4(+) T-lymphocyte counts. To investigate whether the immunoglobulin G (IgG) subclass distribution and avidity of the antibodies produced after vaccination are affected as well, we gave 13 HIV-infected adults with low CD4(+) T-lymphocyte counts (<200 x 10(6)/liter; group I), 11 HIV-infected adults with intermediate CD4(+) T-lymphocyte counts (>/=200 x 10(6)/liter; group II), and 5 healthy controls booster immunizations with tetanus toxoid. The prevaccination antibody concentrations against tetanus toxoid were similar in the HIV-infected and healthy adults. After vaccination the total IgG and the IgG1 anti-tetanus toxoid antibody concentrations were significantly lower in group I than in group II and the controls. The avidity of the IgG1 anti-tetanus toxoid antibodies formed by HIV-infected adults was within the range for healthy controls, irrespective of their CD4(+) T-lymphocyte counts.
Assuntos
Anticorpos Antibacterianos/imunologia , Afinidade de Anticorpos , Infecções por HIV/imunologia , Imunização Secundária , Imunoglobulina G/imunologia , Toxoide Tetânico/imunologia , Adulto , Contagem de Linfócito CD4 , Feminino , Humanos , Isotipos de Imunoglobulinas , Masculino , Pessoa de Meia-Idade , Toxoide Tetânico/administração & dosagemRESUMO
OBJECTIVE: To describe a complication of oral vaccination with live, attenuated poliomyelitis virus in a child infected with HIV. DESIGN: Case report. SETTING: Teaching hospital in Harare, Zimbabwe. SUBJECTS: A boy of 41/2 years and his mother. MAIN OUTCOME MEASURES: Results of clinical and laboratory investigations. RESULTS: Two weeks after receiving the second dose of oral poliomyelitis vaccine during national immunisation days the child developed paralysis of the right leg. He had a high titre of antibodies against poliovirus type 2, as well as antibodies against HIV-1, a low CD4 count, a ratio of CD4 to CD8 count of 0.47, and hypergammaglobulinaemia. He did not have any antibodies against diphtheria, tetanus, or poliovirus types 1 and 3, although he had been given diphtheria, tetanus, and pertussis and oral polio vaccines during his first year and a booster of the diphtheria, tetanus, and pertussis vaccine at 24 months. He had no clinical symptoms of AIDS, but his mother had AIDS and tuberculosis. CONCLUSION: Paralytic poliomyelitis in this child with HIV infection was caused by poliovirus type 2 after oral poliomyelitis vaccine.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Poliomielite/etiologia , Vacina Antipólio de Vírus Inativado/efeitos adversos , Administração Oral , Pré-Escolar , Humanos , Masculino , ZimbábueRESUMO
Immunization with whole-cell pertussis vaccines (WCV) containing heat-killed Bordetella pertussis cells and with acellular vaccines containing genetically or chemically detoxified pertussis toxin (PT) in combination with filamentous hemagglutinin (FHA), pertactin (Prn), or fimbriae confers protection in humans and animals against B. pertussis infection. In an earlier study we demonstrated that FHA is involved in the adherence of these bacteria to human bronchial epithelial cells. In the present study we investigated whether mouse antibodies directed against B. pertussis FHA, PTg, Prn, and fimbriae, or against two other surface molecules, lipopolysaccharide (LPS) and the 40-kDa outer membrane porin protein (OMP), that are not involved in bacterial adherence, were able to block adherence of B. pertussis and B. parapertussis to human bronchial epithelial cells. All antibodies studied inhibited the adherence of B. pertussis to these epithelial cells and were equally effective in this respect. Only antibodies against LPS and 40-kDa OMP affected the adherence of B. parapertussis to epithelial cells. We conclude that antibodies which recognize surface structures on B. pertussis or on B. parapertussis can inhibit adherence of the bacteria to bronchial epithelial cells, irrespective whether these structures play a role in adherence of the bacteria to these cells.
Assuntos
Anticorpos Antibacterianos/imunologia , Aderência Bacteriana , Bordetella pertussis/imunologia , Bordetella/fisiologia , Brônquios/microbiologia , Fatores de Virulência de Bordetella , Adesinas Bacterianas/imunologia , Animais , Anticorpos Monoclonais/imunologia , Bordetella pertussis/patogenicidade , Bordetella pertussis/fisiologia , Linhagem Celular , Hemaglutininas/imunologia , Humanos , Soros Imunes/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Vacina contra Coqueluche/imunologia , VirulênciaRESUMO
During colonization of the respiratory tract by Bordetella pertussis, virulence factors contribute to adherence of the bacterium to the respiratory tract epithelium. In the present study, we examined the roles of the virulence factors filamentous hemagglutinin (FHA), fimbriae, pertactin (Prn), and pertussis toxin (PT) in the adherence of B. pertussis to cells of the human bronchial epithelial cell line NCI-H292 and of the laryngeal epithelial cell line HEp-2. Using B. pertussis mutant strains and purified FHA, fimbriae, Prn, and PT, we demonstrated that both fimbriae and FHA are involved in the adhesion of B. pertussis to laryngeal epithelial cells, whereas only FHA is involved in the adherence to bronchial epithelial cells. For PT and Prn, no role as adhesion factor was found. However, purified PT bound to both bronchial and laryngeal cells and as such reduced the adherence of B. pertussis to these cells. These data may imply that fimbriae play a role in infection of only the laryngeal mucosa, while FHA is the major factor in colonization of the entire respiratory tract.
Assuntos
Aderência Bacteriana , Bordetella pertussis/patogenicidade , Brônquios/microbiologia , Adesinas Bacterianas/fisiologia , Proteínas da Membrana Bacteriana Externa/fisiologia , Bordetella pertussis/fisiologia , Linhagem Celular , Fímbrias Bacterianas/fisiologia , Hemaglutininas/fisiologia , Humanos , Toxina Pertussis , Virulência , Fatores de Virulência de Bordetella/toxicidadeRESUMO
The virulence plasmid-borne genes encoding Yersinia adhesin A (YadA) and several Yersinia secreted proteins (Yops) are involved in the inhibition of phagocytosis and killing of Yersinia enterocolitica by human granulocytes. One of these Yops, YopH, dephosphorylates multiple tyrosine-phosphorylated proteins in eukaryotic cells and is involved in the inhibition of phagocytosis of Y. enterocolitica by human granulocytes. We investigated whether antibody- and complement-opsonized plasmid-bearing (pYV+) Y. enterocolitica inhibits O2- production by human granulocytes in response to various stimuli and whether YopH is involved. Granulocytes were preincubated with mutant strains unable to express YadA or to secrete Yops or YopH. O2- production by granulocytes during stimulation was assessed by measuring the reduction of ferricytochrome c. PYV+ Y. enterocolitica inhibited O2- production by granulocytes incubated with opsonized Y. enterocolitica or N-formyl-Met-Leu-Phe (f-MLP). This inhibitory effect mediated by pYV did not affect receptor-independent O2- production by granulocytes in response to phorbol myristate acetate, indicating that NADPH activity remained unaffected after activation of protein kinase C. The inhibition of f-MLP-induced O2- production by granulocytes depends on the secretion of Yops and not on the expression of YadA. Insertional inactivation of the yopH gene abrogated the inhibition of phagocytosis of antibody- and complement-opsonized Y. enterocolitica by human granulocytes but not of the f-MLP-induced O2- production by granulocytes or tyrosine phosphorylation of granulocyte proteins. These findings suggest that the specific targets for YopH are not present in f-MLP receptor-linked signal transduction and that other Yop-mediated mechanisms are involved.
Assuntos
Proteínas de Bactérias/fisiologia , Granulócitos/metabolismo , Receptores Imunológicos/fisiologia , Receptores de Peptídeos/fisiologia , Superóxidos/metabolismo , Yersinia enterocolitica/fisiologia , Actinas/análise , Adesinas Bacterianas/fisiologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/fisiologia , Genes Bacterianos , Humanos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Fosforilação , Receptores de Formil Peptídeo , Tirosina/metabolismoRESUMO
Interleukin-4 (IL-4), a cytokine produced by T-helper 2 (Th2) cells, can inhibit the development of T-helper 1 (Th1) cells, which results in a decreased release of cytokines by the latter. As interferon-gamma (IFN-gamma), produced by Th1 cells, is involved in the resistance against a Listeria monocytogenes infection, the role of endogenously formed IL-4 during a Listeria infection in mice was investigated. Neutralization of endogenously formed cytokines by subcutaneously injected alginate-encapsulated monoclonal antibody (MoAb)-forming cells results in high antibody titres in the circulation over a long time period. The aim of the present study was to reevaluate the effect of neutralization of IL-4 during a primary Listeria infection and to investigate the role of IL-4 during a secondary infection in mice using encapsulated MoAb-forming cells. During the course of a primary infection in mice given anti-IL-4 antibody-forming cells (anti-IL-4-FC), the number of Listeria found in the liver and spleen was comparable to that found in control mice given anti-beta-galactosidase antibody-forming cells (anti-beta-gal-FC). Activation of macrophages measured by inhibition of Toxoplasma gondii proliferation and the release of reactive nitrogen intermediates (RNI) was not affected by anti-IL-4-FC treatment during infection. Furthermore, during a secondary L. monocytogenes infection the number of bacteria in the liver and spleen of anti-IL-4-treated immune mice was comparable to anti-beta-gal-FC-treated, control, immune mice. The concentration of IFN-gamma in plasma of anti-IL-4-treated immune mice was similar to that of control immune mice. Taken together, these findings demonstrate that neutralization of endogenously formed IL-4 does not affect resistance to a primary or a secondary L. monocytogenes infection in mice.