RESUMEN
A proteome microarray consisting of 992 Schistosoma mansoni proteins was produced and screened with sera to determine antibody signatures indicative of the clinical stages of schistosomiasis and the identification of subunit vaccine candidates. Herein, we describe the methods used to derive the gene list for this array (representing approximately 10% of the predicted S. mansoni proteome). We also probed a pilot version of the microarray with sera from individuals either acutely or chronically infected with S. mansoni from endemic areas in Brazil and sera from individuals resident outside the endemic area (USA) to determine if the array is functional and informative.
Asunto(s)
Proteínas del Helminto/genética , Análisis por Matrices de Proteínas , Proteoma/química , Schistosoma mansoni/química , Esquistosomiasis mansoni/inmunología , Animales , Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/química , Antígenos Helmínticos/genética , Antígenos Helmínticos/inmunología , Biología Computacional , Proteínas del Helminto/química , Proteínas del Helminto/inmunología , Sueros Inmunes/inmunología , Inmunoglobulina G/inmunología , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Proyectos Piloto , Análisis por Matrices de Proteínas/métodos , Proteoma/genética , Proteoma/inmunología , Schistosoma mansoni/genética , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/parasitologíaRESUMEN
We recently completed clinical trials in people with diet-treated celiac disease who were purposefully infected with the ubiquitous human hookworm, Necator americanus. Hookworm infection elicited not only parasite-specific immunity but also modified the host's immune response to gluten. After infection, mucosal IL-1ß and IL-22 responses were enhanced, but IFNγ and IL-17A levels and circulating regulatory T cells following gluten challenge were suppressed, and the adaptive response to gluten acquired a helper T cell type-2 profile. In this review, we briefly, (i) highlight the utility celiac disease offers autoimmune research, (ii) discuss safety and personal experience with N. americanus, (iii) summarise the direct and bystander impact that hookworm infection has on mucosal immunity to the parasite and gluten, respectively, and (iv) speculate why this hookworm's success depends on healing its host and how this might impact on a propensity to autoimmunity.
Asunto(s)
Autoinmunidad , Enfermedad Celíaca/inmunología , Glútenes/inmunología , Necator americanus/inmunología , Animales , Enfermedad Celíaca/parasitología , Enfermedad Celíaca/terapia , Humanos , Necator americanus/fisiología , Terapia con HelmintosRESUMEN
Leishmania major infected BALB/c mice were treated with N-acetyl-l-cysteine (NAC), a glutathione precursor, to evaluate the role of in vivo glutathione on lesion pathology and cytokine profiles following infection. Mice were maintained on NAC-containing water 2 days before infection for a total of 14 weeks. The BALB/c response to L. major infection was improved by oral administration of NAC, at the level of histopathological outcome, lesion progression and cytokine profile. A significantly improved histopathological outcome of the footpad lesion, characterized by a mixed inflammatory infiltrate organized in a focal pattern with little tissue destruction and a reduced parasite load, was observed in NAC-treated BALB/c mice. Histopathological modulation was accompanied by a modified cytokine pattern from popliteal lymph node cells, demonstrated by a sustained higher frequency of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)-producing cells. This work points to an important role for glutathione in the modulation of effector responses in BALB/c mice.