Asunto(s)
Corynebacterium/metabolismo , Toxina Diftérica/química , Toxina Diftérica/metabolismo , Difteria/microbiología , Secuencia de Aminoácidos , Difteria/tratamiento farmacológico , Difteria/epidemiología , Femenino , Alemania/epidemiología , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Homología de Secuencia de AminoácidoRESUMEN
While Corynebacterium ulcerans can mimic classical diphtheria, extrapharyngeal infections are extremely rare. Sequencing of the diphtheria toxin (DT)-encoding tox gene of two C. ulcerans isolates from extrapharyngeal infections revealed differences from C. diphtheriae DT sequences, mainly in the translocation and receptor-binding domains. C. ulcerans supernatants were much less potent than supernatant from C. diphtheriae. A C. ulcerans DT-specific PCR is described below.
Asunto(s)
Corynebacterium/genética , Corynebacterium/patogenicidad , Toxina Diftérica/química , Toxina Diftérica/genética , Mutación , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Infecciones por Corynebacterium/microbiología , Corynebacterium diphtheriae/genética , Corynebacterium diphtheriae/patogenicidad , Células HeLa , Humanos , Masculino , Datos de Secuencia Molecular , Faringitis , Reacción en Cadena de la Polimerasa/métodos , Sinusitis/microbiología , Especificidad de la EspecieRESUMEN
The virulence antigen (LcrV) of pathogenic yersiniae "silences" macrophages against stimulation with the TLR2-agonist zymosan A in a CD14/TLR2-dependent fashion via IL-10 induction. This pathogenically important "silencing" resembles TLR tolerance phenomena; in these, pre-exposure to a primary tolerizing TLR-agonist renders macrophages unresponsive to stimulation with a secondary challenging TLR-agonist which may involve either the same (TLR homotolerance) or a different TLR (TLR heterotolerance) as the primary TLR-agonist. Here, we show that rLcrV induces TLR homo- and heterotolerance against TLR2- or TLR4-agonists both in human and murine macrophages, respectively. The underlying mechanism of LcrV-induced tolerance is most likely not due to changes in TLR2- or TLR4 expression, but involves LcrV-mediated IL-10 production, since LcrV-induced TLR homo- and heterotolerance is highly impaired in IL-10(-/-) macrophages. Moreover, the involvement of IL-10 in TLR tolerance induction seems to be a more general phenomenon as shown by experiments using different TLR-agonists in IL-10(-/-) macrophages. Since LcrV acts as a secreted protein upon macrophages without requiring direct cell contact, as shown in transwell assays, we propose that yersiniae exploit IL-10-involving TLR tolerance mechanisms by the virulence factor LcrV.