RESUMO
Leptospirosis is a severe worldwide zoonotic disease caused by pathogenic Leptospira spp. It has been demonstrated that pathogenic leptospires are resistant to the bactericidal activity of normal human serum while saprophytic strains are susceptible. Pathogenic strains have the ability to bind soluble complement regulators and these activities are thought to contribute to bacterial immune evasion. One strategy used by some pathogens to evade the complement cascade, which is not well explored, is to block the terminal pathway. We have, thus, examined whether leptospires are able to interact with components of the terminal complement pathway. ELISA screening using anti-leptospires serum has shown that the pathogenic, virulent strain L. interrogans L1-130 can bind to immobilized human C8 (1 µg). However, virulent and saprophyte L. biflexa strains showed the ability to interact with C8 and C9, when these components were employed at physiological concentration (50 µg/mL), but the virulent strain seemed more competent. Lsa23, a putative leptospiral adhesin only present in pathogenic strains, interacts with C8 and C9 in a dose-dependent mode, suggesting that this protein could mediate the binding of virulent Leptospira with these components. To our knowledge, this is the first work reporting the binding of Leptospira to C8 and C9 terminal complement components, suggesting that the inhibition of this pathway is part of the strategy used by leptospires to evade the innate immunity.
Assuntos
Proteínas de Bactérias/imunologia , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Leptospira interrogans/imunologia , Leptospira interrogans/metabolismo , Leptospirose/imunologia , Domínios e Motivos de Interação entre Proteínas , Adesinas Bacterianas , Proteínas de Bactérias/genética , Proteínas de Transporte/imunologia , Proteínas de Transporte/metabolismo , Complemento C7/metabolismo , Complemento C8/metabolismo , Complemento C9/metabolismo , Vetores Genéticos , Humanos , Evasão da Resposta Imune , Imunidade Inata , Leptospira interrogans/genética , Leptospira interrogans/patogenicidade , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Proteínas RecombinantesRESUMO
The authors report a case of deficiency of the eighth component of complement in a young adult with a history of three episodes of meningitis; one of them proved to be meningococcal. The literature was reviewed and meningitis due to Neisseria meningitidis strains causing disease in complement-deficient and complement-sufficient patients was demonstrated. Meningococcal disease may be the first manifestation of complement deficiency; screening for complement function must be considered for those with invasive meningococcal disease, with posterior evaluation of the components of the terminal pathway of complement.
Assuntos
Complemento C8/deficiência , Meningite Meningocócica/imunologia , Adulto , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Humanos , Masculino , Meningite Meningocócica/diagnóstico , Meningite Meningocócica/tratamento farmacológico , RecidivaRESUMO
The authors report a case of deficiency of the eighth component of complement in a young adult with a history of three episodes of meningitis; one of them proved to be meningococcal. The literature was reviewed and meningitis due to Neisseria meningitidis strains causing disease in complement-deficient and complement-sufficient patients was demonstrated. Meningococcal disease may be the first manifestation of complement deficiency; screening for complement function must be considered for those with invasive meningococcal disease, with posterior evaluation of the components of the terminal pathway of complement.
Assuntos
Humanos , Masculino , Adulto , Complemento C8 , Meningite Meningocócica , Antibacterianos , Ceftriaxona , Meningite Meningocócica , RecidivaRESUMO
A child who had had meningitis caused by Haemophilus influenzae type b, and then had meningococcal meningitis, was found to have familial deficiency of the beta subunit of the eighth component of complement. The child had not received the H. influenzae type b vaccine. If this deficiency is discovered, we recommend that family members be screened, regardless of their health status.