Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection

• Published in: Cytokine (Philadelphia, Pa.) Vol. 136; p. 155283
• Main Authors: Marcon, Camila Ferreira, Ferreira, Paula Tatiana Mutão, Franco, Priscila Silva, Ribeiro, Mayara, Silva, Rafaela José, Sousa, Roberto Augusto Pereira, Oliveira, Carlo José Freire, Rodrigues Junior, Virmondes, Gomes, Marcos Lucca Moreira, Lazo Chica, Javier Emílio, Mineo, Tiago Wilson Patriarca, Mineo, José Roberto, Barbosa, Bellisa Freitas, Ferro, Eloisa Amália Vieira, Gomes, Angelica Oliveira
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2020
• Subjects: Cytokines; MIF; Morphometry; Pregnancy; Small intestine; Toxoplasma gondii; Pregnancy; Toxoplasma gondii; MIF; Cytokines; Morphometry; Small intestine
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2020.155283

•MIF is up-regulated in gut of pregnant and infected mice.•Pregnancy increases T. gondii parasitism in small intestine.•T. gondii infection changes gut architecture in a way dependent on pregnancy and MIF.•Gut cytokines are modulated by infection, MIF and pregnancy.
Toxoplasma gondii (T. gondii) is an intracellular parasite responsible for causing toxoplasmosis. When infection occurs during pregnancy, it can produce severe congenital infection with ocular and neurologic damage to the infant. From the oral infection parasite reaches the intestine, causing inflammatory response, damage in tissue architecture and systemic dissemination. Macrophage migration inhibition factor (MIF) is a cytokine secreted from both immune and non-immune cells, including gut epithelial cells. MIF is described to promote inflammatory responses, to be associated in colitis pathogenesis and also to play role in maintaining the intestinal barrier. The aim of the present study was to evaluate the influence of the pregnancy and MIF deficiency on T. gondii infection in the intestinal microenvironment and to address how these factors can impact on the intestinal architecture and local cytokine profile. For this purpose, small intestine of pregnant and non-pregnant C57BL/6 MIF deficient mice (MIF−/−) and Wild-type (WT) orally infected with 5 cysts of ME-49 strain of T. gondii were collected on day 8th of infection. Intestines were processed for morphological and morphometric analyses, parasite quantification and for cytokines mensuration. Our results showed that the absence of MIF and pregnancy caused an increase in T. gondii infection index. T. gondii immunolocalization demonstrated that segments preferentially infected with T. gondii were duodenum and ileum. The infection caused a reduction in the size of the intestinal villi, whereas, infection associated with pregnancy caused an increase in villi size due to edema caused by the infection. Also, the goblet cell number was increased in the ileum of MIF−/− mice, when compared to the corresponding WT group. Analyses of cytokine production in the small intestine showed that MIF was up regulated in the gut of pregnant WT mice due to infection. Also, infection provoked an intense Th1 response that was more exacerbated in pregnant MIF−/− mice. We also detected that the Th2/Treg response was more pronounced in MIF−/− mice. Altogether, our results demonstrated that pregnancy and MIF deficiency interferes in the balance of the intestinal cytokines and favors a Th1-immflamatory profile, which in turn, impact in the development of pathology caused by T. gondii infection in the intestinal microenvironment.