RESUMEN
Increasing resistance to anthelmintic drugs indicates a vital need to develop alternative strategies to control helminth infections. Interleukin-3 (IL-3) is a multilineage hematopoietic growth regulator produced by activated T lymphocytes in response to infection. In helminth infections, eosinophils play an important role in the elimination of parasites through their recruitment of inflammatory cells and the release of granules. The ability of IL-3 to stimulate the development of eosinophils makes it a particularly important candidate for therapeutic use to protect against parasites. To enable the role of IL-3 in the development, growth, and differentiation of porcine eosinophils to be elucidated, recombinant IL-3 (rPoIL-3) was expressed and purified. As the amino acid sequence identities between porcine IL-3 and other reported species were quite low ( approximately 39% between human and pig), an assessment of the in vitro activity of rPoIL-3 was made. The culture of porcine bone marrow (BM) cells with rPoIL-3 stimulated the proliferation of SWC3a(hi) myeloid cells, conA rming that rPoIL-3 acted as a hematopoietic cell growth factor. Since rPoIL-3 stimulated the development of myeloid cells in culture, the in vivo potential to produce elevated eosinophil proportions was assessed. In vivo administration of rPoIL-3 induced a signiA cant increase in the number of eosinophils in blood. These results suggest that rPoIL-3 is a potent inducer of eosinophils in swine and supports the inclusion of rPoIL-3 in therapeutic strategies.
Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Eosinófilos/citología , Interleucina-3/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Bovinos , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Humanos , Interleucina-3/inmunología , Recuento de Leucocitos , Ratones , Modelos Biológicos , Conformación Molecular , Enfermedades Parasitarias/sangre , Enfermedades Parasitarias/tratamiento farmacológico , Proteínas Recombinantes/inmunología , Análisis de Secuencia de Proteína , Ovinos , PorcinosRESUMEN
DNA vaccines have great potential but despite the promise shown in rodent models, responses in large animals, including humans, have been disappointing. Furthermore, gene gun delivery of DNA has been used to improve these responses. However, most cells that are transfected are not the professional antigen presenting cells (APC) which are critical for generating the primary immune response. Here, we show that in the large animal model of the pig, the combination of the use of gene gun delivery and a DNA vector that targets antigen presenting cells by expressing a CTLA4-ovalbumin (OVA) fusion antigen, leads to enhanced ovalbumin specific serum IgG, IgA, IgG1 and IgG2 immune responses.
