RESUMEN
Helminth infections have the ability to modulate host's immune response through mechanisms that allow the chronic persistence of the worms in the host. Here, we investigated the mechanisms involved on the suppressive effect of Ascaris suum infection using a murine experimental model of LPS-induced inflammation. We found that infection with A. suum markedly inhibited leucocyte influx induced by LPS into air pouches, suppressed secretion of pro-inflammatory cytokines (IL-1ß, TNF-α and IL-6) and induced high levels of IL-10 and TGF-ß. Augmented frequency of CD4+ CD25high Foxp3+ T cells was observed in the mesenteric lymph nodes of infected mice. Adoptive transfer of purified CD4+ CD25+ T cells to recipient uninfected mice demonstrated that these cells were able to induce a suppressive effect in the LPS-induced inflammation in air pouch model. In addition, adoptive transfer of CD4+ CD25+ T cells derived from IL-10 knockout mice suggests that this suppressive effect of A. suum infection involves IL-10 cytokine. In conclusion, our results demonstrated that A. suum experimental infection was capable of suppressing LPS-induced inflammation by mechanisms, which seem to be dependent on responses of CD4+ CD25+ T cells and secretion of IL-10 cytokine.
Asunto(s)
Ascariasis/inmunología , Ascaris suum/inmunología , Traslado Adoptivo , Animales , Ascariasis/parasitología , Antígenos CD4/metabolismo , Citocinas/metabolismo , Femenino , Factores de Transcripción Forkhead/metabolismo , Inflamación/inducido químicamente , Interleucina-10/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Linfocitos T/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Class II transactivator (CIITA) induces transcription of major histocompatibility complex (MHC) II genes and can potentially be used to improve genetic immunotherapies by converting non-immune cells into cells capable of presenting antigens to CD4+ T cells. However, CIITA expression is tightly controlled and it remains unclear whether distinct non-immune cells differ in this transactivator regulation. Here we describe the development of gene delivery systems capable of promoting the efficient CIITA expression in non-immune cell lines and in primary human cells of an ex vivo skin explant model. Different human cell types undergoing CIITA overexpression presented high-level de novo expression of MHC II, validating the delivery systems as suitable tools for the CIITA evaluation as a molecular adjuvant for gene therapies.
Asunto(s)
Técnicas de Transferencia de Gen , Genes MHC Clase II , Transactivadores/genética , Terapia Genética/métodos , Vectores Genéticos/genética , Células HEK293 , Células HeLa , Humanos , Lentivirus/genética , Piel/metabolismo , Transactivadores/metabolismoRESUMEN
Helminth infections have the ability to modulate host's immune response through mechanisms that allow the chronic persistence of the worms in the host. Here, we investigated the mechanisms involved on the suppressive effect of Ascaris suum infection using a murine experimental model of LPS-induced inflammation. We found that infection with A.suum markedly inhibited leucocyte influx induced by LPS into air pouches, suppressed secretion of pro-inflammatory cytokines (IL-1, TNF- and IL-6) and induced high levels of IL-10 and TGF-. Augmented frequency of CD4(+) CD25(high) Foxp3(+) T cells was observed in the mesenteric lymph nodes of infected mice. Adoptive transfer of purified CD4(+) CD25(+) T cells to recipient uninfected mice demonstrated that these cells were able to induce a suppressive effect in the LPS-induced inflammation in air pouch model. In addition, adoptive transfer of CD4(+) CD25(+) T cells derived from IL-10 knockout mice suggests that this suppressive effect of A.suum infection involves IL-10 cytokine. In conclusion, our results demonstrated that A.suum experimental infection was capable of suppressing LPS-induced inflammation by mechanisms, which seem to be dependent on responses of CD4(+) CD25(+) T cells and secretion of IL-10 cytokine.