Frontiers in Immunology (Oct 2023)

Trypanosoma cruzi P21 recombinant protein modulates Toxoplasma gondii infection in different experimental models of the human maternal–fetal interface

  • Guilherme de Souza,
  • Samuel Cota Teixeira,
  • Aryani Felixa Fajardo Martínez,
  • Rafaela José Silva,
  • Luana Carvalho Luz,
  • Joed Pires de Lima Júnior,
  • Alessandra Monteiro Rosini,
  • Natália Carine Lima dos Santos,
  • Rafael Martins de Oliveira,
  • Marina Paschoalino,
  • Matheus Carvalho Barbosa,
  • Rosiane Nascimento Alves,
  • Angelica Oliveira Gomes,
  • Claudio Vieira da Silva,
  • Eloisa Amália Vieira Ferro,
  • Bellisa Freitas Barbosa

DOI
https://doi.org/10.3389/fimmu.2023.1243480
Journal volume & issue
Vol. 14

Abstract

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IntroductionToxoplasma gondii 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 Trypanosoma cruzi, the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate T. gondii infection.MethodsIn this sense, we aimed to investigate the impact of T. cruzi and recombinant P21 (rP21) on T. gondii infection in BeWo cells and human placental explants.ResultsOur results showed that T. cruzi infection, as well as rP21, increases invasion and decreases intracellular proliferation of T. gondii 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 T. gondii proliferation, whereas T. cruzi infection increases T. gondii 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)-α production.DiscussionIn conclusion, in situations of coinfection, the presence of T. cruzi may favor the congenital transmission of T. gondii, 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 T. gondii infection.

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