AUTHOR=Hernández-de-los-Ríos Alejandro , Murillo-Leon Mateo , Mantilla-Muriel Luz Eliana , Arenas Ailan Farid , Vargas-Montes Mónica , Cardona Néstor , de-la-Torre Alejandra , Sepúlveda-Arias Juan Carlos , Gómez-Marín Jorge Enrique 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2019.00413

DOI=10.3389/fcimb.2019.00413

ISSN=2235-2988

ABSTRACT=<p><italic>Toxoplasma gondii</italic> 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-γ, IL-10, and IL-1β levels in supernatants from PBMCs cultures infected with tachyzoites of the <italic>T. gondii</italic> wild-type RH strain or with knock-out mutants of the <italic>rop16</italic> and <italic>rop18</italic> encoding genes (RHΔ<italic>rop16</italic> and RHΔ<italic>rop18</italic>). Cytokine secretion was compared between PBMCs obtained from seronegative individuals (<italic>n</italic> = 10), with those with chronic asymptomatic (<italic>n</italic> = 8), or ocular infection (<italic>n</italic> = 12). We also evaluated if polymorphisms in the genes encoding for <italic>IFN</italic>-γ, <italic>IL-10, IL-1</italic>β, Toll-like receptor 9 (<italic>TLR9</italic>), and purinoreceptor <italic>P2RX7</italic> influenced the production of the encoded proteins after <italic>ex vivo</italic> stimulation. In individuals with chronic asymptomatic infection, only a moderate effect on IL-10 levels was observed when PBMCs were infected with RHΔ<italic>rop16</italic>, whereas a significant difference in the levels of inflammatory cytokines IFN-γ and IL-1β 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-γ 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.</p>