Author | Pêgo, Beatriz | |
Author | Martinusso, Cesonia A. | |
Author | Bernardazzi, Claudio | |
Author | Ribeiro, Beatriz Elias | |
Author | Cunha, Aline Fernandes de Araujo | |
Author | Mesquita, Jacilene de Souza | |
Author | Nanini, Hayandra F. | |
Author | Machado, Marcelo Pelajo | |
Author | Branco, Morgana T. L. Castelo | |
Author | Cavalcanti, Marta Guimarães | |
Author | Souza, Heitor S. P. de | |
Access date | 2019-09-17T13:51:45Z | |
Available date | 2019-09-17T13:51:45Z | |
Document date | 2019 | |
Citation | PÊGO, Beatriz et al. Schistosoma mansoni Coinfection Attenuates Murine Toxoplasma gondii-Induced Crohn’s-Like Ileitis by Preserving the Epithelial Barrier and Downregulating the Inflammatory Response. Frontiers in Immunology, v. 10, p. 1-16, Mar. 2019. | pt_BR |
ISSN | 1664-3224 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/35632 | |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Co-infecção de Schistosoma Mansoni | pt_BR |
Subject in Portuguese | Imunidade mucosa | pt_BR |
Subject in Portuguese | Doença de Crohn | pt_BR |
Subject in Portuguese | Células de Paneth | pt_BR |
Subject in Portuguese | Barreira epitelial intestinal | pt_BR |
Title | Schistosoma mansoni Coinfection Attenuates Murine Toxoplasma gondii-Induced Crohn's-Like Ileitis by Preserving the Epithelial Barrier and Downregulating the Inflammatory Response | pt_BR |
Type | Article | pt_BR |
DOI | 10.3389/fimmu.2019.00442 | |
Abstract | 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. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Medicina Interna. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Medicina Interna. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Medicina Interna. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Medicina Interna. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Laboratório de Microbiologia e Parasitologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Medicina Interna. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Patologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Clínica de Doenças Infeciosas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Medicina Interna. Rio de Janeiro, RJ, Brasil / Instituto D´Or de Pesquisa e Educação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | S. mansoni coinfection | pt_BR |
Subject | T. gondii-induced ileitis | pt_BR |
Subject | Mucosal immunity | pt_BR |
Subject | Paneth cells | pt_BR |
Subject | Intestinal epithelial barrieR | pt_BR |
Subject | Crohn’s disease | pt_BR |