AI Article Synopsis

  • * The study focused on a specific surface antigen of the parasite, P18, which affects its ability to invade macrophages, and found that a deletion of this gene reduced virulence and increased inflammatory responses in infected mice.
  • * The research suggests that P18 plays a crucial role in how the parasite interacts with the immune system, particularly influencing the response to interferon-gamma (IFN-γ) and the transition between dormant and active parasite forms.

Article Abstract

Toxoplasmosis is a prevalent parasitic disease caused by (). Under the control of the host immune system, 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 gene (KO ) 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 , 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 resulted in a higher number of bradyzoite cysts, and a stronger inflammatory response. A prolonged survival of mice was observed upon immunosuppression of KO 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 , 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273438PMC
http://dx.doi.org/10.3389/fimmu.2021.643292DOI Listing

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