AsianScientist (Sep. 15, 2015) – A group of researchers in Osaka University’s Research Institute for Microbial Diseases have identified a host molecule, RabGDIα, that suppresses the immune reaction to the pathogenic parasite Toxoplasma gondii. Their work, led by Professor Yamamoto Masahiro and published in Proceedings of the National Academy of Sciences, also showed that the suppression of RabGDIα drastically enhanced immune reaction to T. gondii.
T. gondii is mainly transmitted to humans by eating undercooked infected meat and can cause fatal encephalosis and myocarditis in patients with immunodeficiency under the treatment of AIDS or anticancer drug treatment. In pregnant women, T. gondii can cause complications leading to miscarriage or birth defects.
The host immune system typically counters T. gondii infection by launching an interferon-gamma (IFN-γ)-dependent immune response. T. gondii are known to be able to suppress the immune system and escape detection, although the mechanism is not well understood.
To study the mechanism involved in host immune reaction to T. gondii, the authors removed RabGDIα gene in mouse experimental model and studied their immune responses. They observed that removal of RabGDIα from the host drastically increased IFN-γ-dependent immune response that destroys Toxoplasma, resulting in a decreased number of Toxoplasma gondii in the bloodstream.
Moreover, even in infection with a higher than usual dose of T. gondii, the survival rate of RabGDIα-deficient mice is high and the degree of fatal encephalosis is not serious. Lastly, they managed to identify the portion of RabGDIα that is essential for its suppression function: the hydrophobic lipid-binding pocket.
This group’s research results showed that suppression of RabGDIα function drastically increased the immune response to T. gondii and reduced the serious complication of Toxoplasma encephalopathy. The authors suggest that targeting RabGDIα might be a promising line of T. gondii treatment.
The article can be found at: Ohshima et al. (2015) RabGDIα is a Negative Regulator of Interferon-γ-inducible GTPase-Dependent Cell-Autonomous Immunity to Toxoplasma gondii.
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Source: Osaka University.
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