Influence of Two Major Toxoplasma Gondii Virulence Factors (ROP16 and ROP18) on the Immune Response of Peripheral Blood Mononuclear Cells to Human Toxoplasmosis Infection

Toxoplasma gondii ROP16 and ROP18 proteins have been identified as important virulence factors for this parasite. Here, we describe the effect of ROP16 and ROP18 proteins on peripheral blood mononuclear cells (PBMCs) from individuals with different clinical status of infection. We evaluated IFN-?, IL-10, and IL-1? levels in supernatants from PBMCs cultures infected with tachyzoites of the T. gondii wild-type RH strain or with knock-out mutants of the rop16 and rop18 encoding genes (RH?rop16 and RH?rop18). Cytokine secretion was compared between PBMCs obtained from seronegative individuals (n = 10), with those with chronic asymptomatic (n = 8), or ocular infection (n = 12). We also evaluated if polymorphisms in the genes encoding for IFN-?, IL-10, IL-1?, Toll-like receptor 9 (TLR9), and purinoreceptor P2RX7 influenced the production of the encoded proteins after ex vivo stimulation. In individuals with chronic asymptomatic infection, only a moderate effect on IL-10 levels was observed when PBMCs were infected with RH?rop16, whereas a significant difference in the levels of inflammatory cytokines IFN-? and IL-1? was observed in seronegative individuals, but this was also dependent on the host's cytokine gene polymorphisms. Infection with ROP16-deficient parasites had a significant effect on IFN-? production in previously non-infected individuals, suggesting that ROP16 which is considered as a virulence factor plays a role during the primary infection in humans, but not in the secondary immune response. © Copyright © 2019 Hernández-de-los-Ríos, Murillo-Leon, Mantilla-Muriel, Arenas, Vargas-Montes, Cardona, de-la-Torre, Sepúlveda-Arias and Gómez-Marín.

• Fecha de publicación: 2019
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/24080
• Acceso en línea: https://doi.org/10.3389/fcimb.2019.00413; https://repository.urosario.edu.co/handle/10336/24080
• Palabra clave: Gamma interferon; Interleukin 10; Interleukin 1beta; Purinergic p2y2 receptor; Rop16 protein; Rop18 protein; Stat3 protein; Stat6 protein; Toll like receptor 9; Unclassified drug; Virulence factor; Adult; Article; Asymptomatic infection; Clinical article; Controlled study; Cytokine release; Enzyme linked immunosorbent assay; Eye infection; Female; Gene expression; Gene knockout; Human; Human cell; Immune response; Inflammation; Male; Nonhuman; Ocular toxoplasmosis; Ophthalmoscopy; Parasite virulence; Peripheral blood mononuclear cell; Protein expression; Protein phosphorylation; Single nucleotide polymorphism; Tachyzoite; Toxoplasma gondii; Toxoplasmosis; Western blotting; Cytokines; Ocular toxoplasmosis; Peripheral blood mononuclear cells; Polymorphisms; Rop16 protein; Rop18 protein; Toxoplasma
• License: Abierto (Texto Completo)