RESUMEN
BACKGROUND: Reports of leishmaniasis in immunosuppressed patients after visiting the Mediterranean Basin are becoming increasingly common. Still, awareness of the risk of infection and its clinical manifestations may be insufficient among healthcare professionals in the travellers' home countries. METHODS: This observational, longitudinal study included 47 patients from Sweden with rheumatic disease and ongoing immunomodulatory treatment, who visited a rehabilitation centre in southern Spain where leishmaniasis is endemic. Patients were evaluated for clinical signs of leishmaniasis at baseline and after three years. Patients with leishmaniasis were followed for 4-5 years. The treatment outcome was assessed by clinical evaluation and determination of the cell-mediated immunological response to Leishmania by a whole blood cytokine release assay. RESULTS: Seven patients (15%) were diagnosed with leishmaniasis. The median time from exposure to the onset of symptoms was 3 [1-17] months. The median delay between the onset of symptoms and treatment start was 9 [1-12] months. All patients with leishmaniasis responded well to treatment. Only one patient had a relapse, which occurred within the first year. CONCLUSION: Healthcare professionals need to be aware of the increased risk of leishmaniasis for travellers who are immunosuppressed. Knowledge of the symptoms is crucial for a timely diagnosis and early treatment.
Asunto(s)
Leishmania infantum , Leishmaniasis Visceral , Leishmaniasis , Humanos , España/epidemiología , Estudios Longitudinales , Estudios de Cohortes , Leishmaniasis/complicaciones , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/epidemiologíaRESUMEN
Staphylococcus aureus infection triggers polyclonal B-cell activation. It was sought to further characterize the hypergammaglobulinemia seen in Staphylococcus aureus infection, focusing on the significance of protease-specific B-cell responses. Sera from mice infected with Staphylococcus aureus wild-type strain 8325-4 and two of its isogenic mutants devoid of protease expression were analyzed for the occurrence of polyclonal B-cell activation and the presence of specific antibodies against a set of exoproteases and superantigens. Furthermore, the functional properties of anti-V8-protease antibodies were analyzed in vitro. Polyclonal activation was manifested by increased levels of total serum IgG and IgM in all infected animals and by antibodies to staphylococcal toxins and aureolysin whether these antigens were present in the inoculate or not. Importantly, Staphylococcus aureus mutant lacking the V8-protease did not trigger a response against this enzyme. In contrast, strains expressing the V8-protease elicited V8-protease antibodies, proving the antigen-specific nature of this response. In vitro tests revealed that these antibodies had the capacity to inhibit the V8 protease activity in a dose-dependent manner. It was concluded that exposure to Staphylococcus aureus, in addition to a massive polyclonal B-cell response, gives rise to production of exoprotease-specific antibodies displaying functional properties.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/inmunología , Péptido Hidrolasas/inmunología , Staphylococcus aureus/inmunología , Animales , Linfocitos B/inmunología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Femenino , Eliminación de Gen , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Metaloendopeptidasas/inmunología , Ratones , Pruebas de Neutralización , Péptido Hidrolasas/genética , Péptido Hidrolasas/metabolismo , Staphylococcus aureus/genética , Superantígenos/inmunologíaRESUMEN
Matrix metalloproteinases constitute a family of structurally related endopeptidases that are crucial for the normal turnover of the extracellular matrix. Elevated levels of MMP-9 have been demonstrated in synovial fluids of rheumatoid arthritis patients, and a correlation with the severity of the disease has been described. The aim of this study was to explore the impact of MMP-9 expression on joint inflammation and destruction in a model of bacterially induced septic arthritis. MMP-9 knock-out mice and C57Bl6 congenic controls were inoculated intravenously or intra-articularly with Staphylococcus aureus. Arthritis was evaluated clinically and by means of histology. Zymographic analyses were performed to study ex vivo induction of MMP-9 following exposure to S. aureus. The MMP-9 knock-out mice displayed a significantly higher frequency and severity, but not destructivity, of arthritis than did the wild-type mice. The knock-out mice also proved to harbour an increased number of bacteria locally in joints and systemically in kidneys, possibly by impaired extravasation and recruitment of leukocytes and a deficient early defence against infection. Our findings indicate that deficiency in MMP-9 increases the degree of joint inflammation due to decreased bacterial clearance.
Asunto(s)
Artritis Infecciosa/enzimología , Artritis Infecciosa/microbiología , Metaloproteinasa 9 de la Matriz/deficiencia , Infecciones Estafilocócicas/enzimología , Staphylococcus aureus/inmunología , Animales , Artritis Infecciosa/inmunología , Artritis Infecciosa/patología , Procesos de Crecimiento Celular/fisiología , Modelos Animales de Enfermedad , Electroforesis en Gel de Poliacrilamida , Femenino , Histocitoquímica , Interleucina-6/metabolismo , Articulaciones/enzimología , Articulaciones/inmunología , Articulaciones/microbiología , Articulaciones/patología , Metaloproteinasa 9 de la Matriz/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiologíaRESUMEN
The exoproteases of Staphylococcus aureus have been proposed as virulence factors during S. aureus infections. To investigate this, we used the wild-type S. aureus strain 8325-4 and its mutants devoid of aureolysin, serine protease, and cysteine protease, respectively, in a well-established model of septic arthritis in mice. The inactivation of the exoprotease genes did not affect the frequency or the severity of joint disease. We conclude that in the model of haematogenously spread staphylococcal arthritis, the bacterial proteases studied do not act as virulence factors.
Asunto(s)
Artritis Infecciosa/microbiología , Cisteína Endopeptidasas/genética , Serina Endopeptidasas/toxicidad , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/patogenicidad , Animales , Artritis Infecciosa/patología , Modelos Animales de Enfermedad , Femenino , Regulación Enzimológica de la Expresión Génica , Genes Bacterianos , Ratones , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Staphylococcus aureus/enzimología , Staphylococcus aureus/genética , Factores de Virulencia/toxicidadRESUMEN
BACKGROUND: Psoriasis is a chronic inflammatory disease that is manifested on the skin. Studies of oral health in psoriasis patients are limited. The aim of this study is to assess the experience and risk of caries and periodontal disease in individuals with and without psoriasis. METHODS: The material consisted of 89 individuals with mild-to-moderate chronic plaque psoriasis and 54 without psoriasis, recruited at the University Hospital in Gothenburg, Gothenburg, Sweden. Psoriatic arthritis (PsoA) was diagnosed in 25 of the individuals with psoriasis. All participants answered questionnaires and were subjected to saliva sampling and oral radiologic and clinical examinations. Two computer applications were used for illustration of oral disease risk profiles. RESULTS: Individuals with psoriasis had lower salivary pH, fewer remaining teeth, fewer sites with probing depth ≤4 mm, and a lower radiographic alveolar bone level than individuals without psoriasis (P <0.05). Most of the differences remained significant after controlling for confounders. Differences in alveolar bone levels were no longer significant, particularly after introducing the confounder sex into the regression model. Similar numbers of decayed and filled teeth, sites with deep pockets, sites that bled on probing, and risk profiles were observed. Individuals with PsoA exhibited a lower stimulated salivary secretion rate than those without psoriasis (P <0.05). CONCLUSIONS: There were no differences in profiles of caries and periodontal disease experience and risk between individuals with and without psoriasis. Fewer remaining teeth were observed in individuals with psoriasis. However, the exact reason for tooth loss could not be identified. Meanwhile, the reduced salivary pH in individuals with psoriasis and salivary secretion in individuals with PsoA may pose some risk for future caries.
Asunto(s)
Caries Dental/complicaciones , Periodontitis/complicaciones , Psoriasis/complicaciones , Pérdida de Diente/complicaciones , Adulto , Anciano , Análisis de Varianza , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Índice CPO , Caries Dental/patología , Femenino , Humanos , Concentración de Iones de Hidrógeno , Lactobacillus/aislamiento & purificación , Modelos Lineales , Masculino , Persona de Mediana Edad , Índice Periodontal , Bolsa Periodontal/complicaciones , Bolsa Periodontal/patología , Periodontitis/patología , Factores de Riesgo , Saliva/química , Saliva/metabolismo , Saliva/microbiología , Factores Sexuales , Fumar , Streptococcus mutans/aislamiento & purificaciónRESUMEN
Proteases of Staphylococcus aureus have long been considered to function as important virulence factors, although direct evidence of the role of particular enzymes remains incomplete and elusive. Here, we sought to provide a collective view of the prevalence of extracellular protease genes in genomes of commensal and pathogenic strains of S. aureus and their expression in the course of human and mouse infection. Data on V8 protease, staphopains A and B, aureolysin, and the recently described and poorly characterized group of six Spl proteases are provided. A phylogenetically diverse collection of 167 clinical isolates was analyzed, resulting in the comprehensive genetic survey of the prevalence of protease-encoding genes. No correlation between identified gene patterns with specific infections was established. Humoral response against the proteases of interest was examined in the sera derived from human patients and from a model mouse infection. The analysis suggests that at least some, if not all, tested proteases are expressed and secreted during the course of infection. Overall, the results presented in this study support the hypothesis that the secretory proteases as a group may contribute to the virulence of S. aureus.