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KMID : 0425120200580010007
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Parasites, Hosts and Diseases
2020 Volume.58 No. 1 p.7 ~ p.14
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4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages
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Lee Ji-Na
Choi Jae-Won
Han Hye-Young
Kim Woo-Sik
Song Ha-Yeon
Byun Eui-Baek
Byun Eui-Hong
Lee Young-Ha
Yuk Jae-Min
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Abstract
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Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human popu- lation worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effec- tive drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4- HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expres- sion of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1- mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.
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KEYWORD
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Toxoplasma gondii, toxoplasmosis, autophagy, sirtinol, 4-hydroxybenzaldehyde, NAD-dependent protein deacetylase sirtuin-1, LC3-phosphatidylethanolamine conjugate
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