Author:
de Souza Guilherme,Teixeira Samuel Cota,Fajardo Martínez Aryani Felixa,Silva Rafaela José,Luz Luana Carvalho,Lima Júnior Joed Pires de,Rosini Alessandra Monteiro,dos Santos Natália Carine Lima,de Oliveira Rafael Martins,Paschoalino Marina,Barbosa Matheus Carvalho,Alves Rosiane Nascimento,Gomes Angelica Oliveira,da Silva Claudio Vieira,Ferro Eloisa Amália Vieira,Barbosa Bellisa Freitas
Abstract
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.
Funder
Fundação de Amparo à Pesquisa do Estado de Minas Gerais
Conselho Nacional de Desenvolvimento CientÌfico e Tecnològico
Coordenação de Aperfeiçoamento de Pessoal de NÌvel Superior
Subject
Immunology,Immunology and Allergy
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