RESUMO
Background and aims: Mice orally infected with T. gondii develop Crohn's disease (CD)-like enteritis associated with severe mucosal damage and a systemic inflammatory response, resulting in high morbidity and mortality. Previously, helminthic infections have shown therapeutic potential in experimental colitis. However, the role of S. mansoni in T. gondii-induced CD-like enteritis has not been elucidated. Our study investigated the mechanisms underlying T. gondii-induced ileitis and the potential therapeutic effect of S. mansoni coinfection. Methods: C57BL/6 mice were infected by subcutaneous injection of cercariae of the BH strain of S. mansoni, and 7-9 weeks later, they were orally infected with cysts of the ME49 strain of T. gondii. After euthanasia, the ileum was removed for histopathological analysis; staining for goblet cells; immunohistochemistry characterizing mononuclear cells, lysozyme expression, apoptotic cells, and intracellular pathway activation; and measuring gene expression levels by real-time PCR. Cytokine concentrations were measured in the serial serum samples and culture supernatants of the ileal explants, in addition to myeloperoxidase (MPO) activity. Results:T. gondii-monoinfected mice presented dense inflammatory cell infiltrates and ulcerations in the terminal ileum, with abundant cell extrusion, apoptotic bodies, and necrosis; these effects were absent in S. mansoni-infected or coinfected animals. Coinfection preserved goblet cells and Paneth cells, remarkably depleted in T. gondii-infected mice. Densities of CD4- and CD11b-positive cells were increased in T. gondii- compared to S. mansoni-infected mice and controls. MPO was significantly increased among T. gondii-mice, while attenuated in coinfected animals. In T. gondii-infected mice, the culture supernatants of the explants showed increased concentrations of TNF-alpha, IFN-gamma, and IL-17, and the ileal tissue revealed increased expression of the mRNA transcripts for IL-1 beta, NOS2, HMOX1, MMP3, and MMP9 and activation of NF-kappa B and p38 MAPK signaling, all of which were counterregulated by S. mansoni coinfection. Conclusion:S. mansoni coinfection attenuates T. gondii-induced ileitis by preserving mucosal integrity and downregulating the local inflammatory response based on the activation of NF-kappa B and MAPK. The protective function of prior S. mansoni infection suggests the involvement of innate immune mechanisms and supports a conceptually new approach to the treatment of chronic inflammatory diseases, including CD.
Assuntos
Coinfecção/imunologia , Ileíte/prevenção & controle , Mucosa Intestinal/fisiopatologia , Esquistossomose mansoni/imunologia , Terapia com Helmintos , Toxoplasmose Animal/terapia , Animais , Apoptose , Doença de Crohn/terapia , Citocinas/sangue , Modelos Animais de Doenças , Regulação para Baixo , Epitélio/fisiologia , Perfilação da Expressão Gênica , Ileíte/etiologia , Ileíte/imunologia , Ileíte/patologia , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Peroxidase/sangue , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Toxoplasmose Animal/complicações , Toxoplasmose Animal/imunologiaRESUMO
BACKGROUND: There are substantial evidences suggesting that probiotics can protect the gastrointestinal tract against inflammatory or infectious episodes. The effects of oral treatment with viable or heat-killed cells of Saccharomyces boulardii (Sb) on bacterial translocation, intestinal permeability, histological aspect of the ileum, and some immunological parameters were evaluated in a murine intestinal obstruction (IO) model. RESULTS: Bacterial translocation and intestinal permeability in the IO group were significantly higher when compared to a Sham group (p < 0.05). Pretreatment with both viable and heat-killed S. boulardii prevented these increases, and the data obtained for IO + Sb and IO + heat-killed Sb groups were similar to those observed in the Sham group (p > 0.05). Histological analysis showed preservation of the ileum mucosa in mice that received both forms of the yeast when compared to the lesions observed in the IO group. The levels of serum interleukin (IL)-10 and intestinal secretory immunoglobulin A (sIgA) were higher in the animals that received both yeast treatments when compared to those from IO and Sham groups. CONCLUSION: Oral treatment with viable or heat-killed cells of S. boulardii maintained intestinal integrity and modulated the immune system in a murine IO model, preventing bacterial translocation and intestinal lesions.