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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> is the etiologic agent of toxoplasmosis, a disease that affects about one-third of the human population. Most infected individuals are asymptomatic, but severe cases can occur such as in congenital transmission, which can be aggravated in individuals infected with other pathogens, such as HIV-positive pregnant women. However, it is unknown whether infection by other pathogens, such as <jats:italic>Trypanosoma cruzi<\/jats:italic>, the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate <jats:italic>T. gondii<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this sense, we aimed to investigate the impact of <jats:italic>T. cruzi<\/jats:italic> and recombinant P21 (rP21) on <jats:italic>T. gondii<\/jats:italic> infection in BeWo cells and human placental explants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed that <jats:italic>T. cruzi<\/jats:italic> infection, as well as rP21, increases invasion and decreases intracellular proliferation of <jats:italic>T. gondii<\/jats:italic> in BeWo cells. The increase in invasion promoted by rP21 is dependent on its binding to CXCR4 and the actin cytoskeleton polymerization, while the decrease in proliferation is due to an arrest in the S\/M phase in the parasite cell cycle, as well as interleukin (IL)-6 upregulation and IL-8 downmodulation. On the other hand, in human placental villi, rP21 can either increase or decrease <jats:italic>T. gondii<\/jats:italic> proliferation, whereas <jats:italic>T. cruzi<\/jats:italic> infection increases <jats:italic>T. gondii<\/jats:italic> proliferation. This increase can be explained by the induction of an anti-inflammatory environment through an increase in IL-4 and a decrease in IL-6, IL-8, macrophage migration inhibitory factor (MIF), and tumor necrosis factor (TNF)-\u03b1 production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, in situations of coinfection, the presence of <jats:italic>T. cruzi<\/jats:italic> may favor the congenital transmission of <jats:italic>T. gondii<\/jats:italic>, highlighting the importance of neonatal screening for both diseases, as well as the importance of studies with P21 as a future therapeutic target for the treatment of Chagas disease, since it can also favor <jats:italic>T. gondii<\/jats:italic> infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1243480","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T05:50:18Z","timestamp":1697435418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Trypanosoma cruzi P21 recombinant protein modulates Toxoplasma gondii infection in different experimental models of the human maternal\u2013fetal interface"],"prefix":"10.3389","volume":"14","author":[{"given":"Guilherme","family":"de Souza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Cota","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryani Felixa","family":"Fajardo Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela 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