Targeting p62 As A Possible Toxoplasma Vaccine

Scientists have discovered that the autophagy receptor p62 plays a key role in activating the killer T cells during infection with T. gondii.

AsianScientist (Nov. 4, 2015) – Researchers have identified a key host molecule that can control the immune response to the pathogenic parasite, Toxoplasma gondii. Their findings, published in Cell Reports, could offer new strategies for developing an inactivated toxoplasma vaccine.

T. gondii is a common parasite which causes the development of fatal encephalosis or pneumonia in immunodeficient patients under treatment of AIDS or cancer. Pregnant women who are infected may suffer a miscarriage or the newborn child may suffer from a congenital disease. Currently, a toxoplasma vaccine for humans is not available. Using experimental animals such as mice, basic research for developing an inactivated vaccine is underway.

A prior study found that the antigens derived from the toxoplasma emitted within the parasitophorous vacuole become the major antigens for the killer T cells. In the present study led by Professor Masahiro Yamamoto from Osaka University, researchers investigated the activation of killer T cells when the toxoplasma-infected cells were stimulated by interferon-γ (IFN-γ).

They found that the activity of antigen-specific killer T cells in infected cells that were stimulated by IFN-γ was dramatically higher than in non-stimulated infected cells. This robust activation of killer T cells seen when these infected cells undergo IFN-γ stimulation was significantly reduced in mice which lacked the host molecule p62.

Even on an individual level, when compared with wild-type mice, there was a sharp decrease in antigen-specific killer T cells in p62 deficient mice when administered the toxoplasma-inactivated vaccine.

These findings demonstrate that IFN-γ-dependent p62 has the unique role of gathering in the parasitophorous vacuole of toxoplasma through IFN-γ stimulation and activating the antigen-specific killer T cells released within the parasitophorous vacuole.

The article can be found at: Lee et al. (2015) p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen.

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Source: Osaka University.
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