P2X7 Receptor Modulation of the Gut Microbiota and the Inflammasome Determines the Severity of IToxoplasma gondii/I-Induced Ileitis

• Published in: Biomedicines 2023-02, Vol.11 (2)
• Main Authors: Moreira-Souza, Aline Cristina Abreu, Nanini, Hayandra Ferreira, Rangel, Thuany Prado, da Silva, Sthefani Rodrigues Batista, Damasceno, Beatriz Pêgo, Ribeiro, Beatriz Elias, Cascabulho, Cynthia M, Thompson, Fabiano, Leal, Camille, Santana, Patrícia Teixeira, Rosas, Siane Lopes Bittencourt, de Andrade, Kívia Queiroz, Silva, Claudia L. Ma, Vommaro, Rossiane Claudia, de Souza, Heitor Siffert Pereira, Coutinho-Silva, Robson
• Format: Article
• Language: English
• Subjects: Health aspects; Toxoplasma
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11020555

In mice, oral Toxoplasma gondii infection induces severe ileitis. The aim of the present study was to investigate the impact of the P2X7 receptor (P2X7) on the inflammatory response to T. gondii-induced ileitis. Cysts of the ME49 strain of T. gondii were used to induce ileitis. The infected mice were euthanized on day 8 and ileal tissue and peripheral blood were collected for histopathological and immunohistochemical analyses. Ileal contractility, inflammatory mediators, inflammasome activation, quantitative PCR analysis of gene expression, and fecal microbiota were assessed using appropriate techniques, respectively. The infected P2X7−/− mice had greater disease severity, parasitic burden, liver damage, and intestinal contractility than the infected wild-type (WT) mice. Infection increased serum IL-6 and IFN-γ and tissue caspase-1 but not NLRP3 in P2X7−/− mice compared to WT mice. Bacteroidaceae, Rikenellaceae, and Rhodospirillales increased while Muribaculaceae and Lactobacillaceae decreased in the infected WT and P2X7−/− mice. Bacteroidia and Tannerellaceae increased in the P2X7−/− mice with ileitis. By contrast, Clostridiales and Mollicutes were absent in the P2X7−/− mice but increased in the WT mice. P2X7 protects mice against T. gondii infection by activating the inflammasome and regulating the local and systemic immune responses. Specific gut bacterial populations modulated by P2X7 determine disease severity.