AUTHOR=Hamie Maguy , Tawil Nadim , El Hajj Rana , Najm Rania , Moodad Sara , Hleihel Rita , Karam Martin , El Sayyed Sana , Besteiro Sébastien , El-Sabban Marwan , Dubremetz Jean-Francois , Lebrun Maryse , El Hajj Hiba 

TITLE=P18 (SRS35/TgSAG4) Plays a Role in the Invasion and Virulence of Toxoplasma gondii

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.643292

DOI=10.3389/fimmu.2021.643292

ISSN=1664-3224

ABSTRACT=<p>Toxoplasmosis is a prevalent parasitic disease caused by <italic>Toxoplasma gondii</italic> (<italic>T. gondii</italic>). Under the control of the host immune system, <italic>T. gondii</italic> persists as latent bradyzoite cysts. Immunosuppression leads to their reactivation, a potentially life-threatening condition. Interferon-gamma (IFN-γ) controls the different stages of toxoplasmosis. Here, we addressed the role of the parasite surface antigen P18, belonging to the Surface-Antigen 1 (SAG-1) Related Sequence (SRS) family, in a cyst-forming strain. Deletion of <italic>P18</italic> gene (KO <italic>P18</italic>) impaired the invasion of parasites in macrophages and IFN-γ-mediated activation of macrophages further reduced the invasion capacity of this KO, as compared to WT strain. Mice infected by KO <italic>P18</italic>, showed a marked decrease in virulence during acute toxoplasmosis. This was consequent to less parasitemia, accompanied by a substantial recruitment of dendritic cells, macrophages and natural killer cells (NK). Furthermore, KO <italic>P18</italic> resulted in a higher number of bradyzoite cysts, and a stronger inflammatory response. A prolonged survival of mice was observed upon immunosuppression of KO <italic>P18</italic> infected BALB/c mice or upon oral infection of Severe Combined Immunodeficiency (SCID) mice, with intact macrophages and natural killer (NK) cells. In stark contrast, oral infection of NSG (NOD/Shi-scid/IL-2Rγnull) mice, defective in macrophages and NK cells, with <italic>KO P18</italic>, was as lethal as that of the control strain showing that the conversion from bradyzoites to tachyzoites is intact and, suggesting a role of P18 in the response to host IFN-γ. Collectively, these data demonstrate a role for P18 surface antigen in the invasion of macrophages and in the virulence of the parasite, during acute and chronic toxoplasmosis.</p>