Polymorphisms of the TLR4 gene: Risk factor for chronicity and severity in oral vectorial Chagas disease.

Autor: Sánchez G; Sección Inmunogenética, Laboratorio de Fisiopatología, Centro de Medicina Experimental. Instituto Venezolano de Investigaciones Científicas, Altos de Pipe, Edo, Apto 1020, Miranda, Venezuela., Salazar-Alcalá E; Sección Inmunogenética, Laboratorio de Fisiopatología, Centro de Medicina Experimental. Instituto Venezolano de Investigaciones Científicas, Altos de Pipe, Edo, Apto 1020, Miranda, Venezuela., Hernández F; Sección Inmunogenética, Laboratorio de Fisiopatología, Centro de Medicina Experimental. Instituto Venezolano de Investigaciones Científicas, Altos de Pipe, Edo, Apto 1020, Miranda, Venezuela. Electronic address: mfernand@ivic.gob.ve., Deglesne PA; Sección Inmunogenética, Laboratorio de Fisiopatología, Centro de Medicina Experimental. Instituto Venezolano de Investigaciones Científicas, Altos de Pipe, Edo, Apto 1020, Miranda, Venezuela., Bello ZD; Sección de Inmunología, Instituto de Medicina Tropical. Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela., de Noya BA; Sección de Inmunología, Instituto de Medicina Tropical. Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela., Noya O; Sección de Biohelmintiasis, Instituto de Medicina Tropical. Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela., Fernández-Mestre M; Sección Inmunogenética, Laboratorio de Fisiopatología, Centro de Medicina Experimental. Instituto Venezolano de Investigaciones Científicas, Altos de Pipe, Edo, Apto 1020, Miranda, Venezuela. Electronic address: mfernandezmestre@gmail.com.
Jazyk: angličtina
Zdroj: Experimental parasitology [Exp Parasitol] 2022 Jul; Vol. 238, pp. 108243. Date of Electronic Publication: 2022 Mar 10.
DOI: 10.1016/j.exppara.2022.108243
Abstrakt: Chagas disease is one of the parasitic infections with the greatest socio-economic impact in Latin America. In Venezuela, epidemiological data has shown different sources of infection, such as the vectorial route by oral transmission. Given the importance of the TLR4 gene in the innate immune response triggered by infection with Trypanosoma cruzi, this work analyses the role of TLR4 polymorphisms and its possible effect on cytokine expression. Genomic DNA was extracted from the peripheral blood of patients from the main outbreak of oral Chagas disease in Venezuela (n = 90), as well as from a group of healthy individuals (n = 183). Subsequently, peripheral blood was also extracted from individuals with different TLR4 haplotypes and then stimulated with LPS to determine the cytokine concentration by ELISA. The internalization of TLR4 was evaluated by flow cytometry. In comparison to healthy individuals, the analysis showed a significantly increased frequency of the Asp/Gly genotype in symptomatic patients. Also, observed a correlation of the 299/399 haplotype with a significant decrease in cytokine concentration and disease severity. Finally, the parasites' trypomastigotes cause the internalization or negative regulation of TLR4. The variants of TLR4 associated with low production of cytokines may be a risk factor for chronicity and severity (cardiac involvement) in oral vectorial Chagas disease.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: