Dendritic cell is one of the first innate immune cell to encounter T. gondii after the parasite crosses the host intestinal epithelium. T. gondii requires intact DC as a carrier to infiltrate into host central nervous system (CNS) without being detected or eliminated by host defense system. The mechanism by which T. gondii avoids innate immune defense of host cell, especially in the dendritic cell is unknown. Therefore, we examined the role of host PI3K/AKT signaling pathway activation by T. gondii in dendritic cell. T. gondii infection or T. gondii excretory/secretory antigen (TgESA) treatment to the murine dendritic cell line DC2.4 induced AKT phosphorylation, and treatment of PI3K inhibitors effectively suppressed the T. gondii proliferation but had no effect on infection rate or invasion rate. Furthermore, it is found that T. gondii or TgESA can reduce H2O2-induced intracellular reactive oxygen species (ROS) as well as host endogenous ROS via PI3K/AKT pathway activation. While searching for the main source of the ROS, we found that NADPH oxidase 4 (NOX4) expression was controlled by T. gondii infection or TgESA treatment, which is in correlation with previous observation of the ROS reduction by identical treatments. These findings suggest that the manipulation of the host PI3K/AKT signaling pathway and NOX4 expression is an essential mechanism for the down-regulation of ROS, and therefore, for the survival and the proliferation of T. gondii.
Citations
Citations to this article as recorded by
Small molecule kinase inhibitor altiratinib inhibits brain cyst forming bradyzoites of Toxoplasma gondii Yeong Hoon Kim, Hye-Jin Ahn, Hwa Sun Kim, Ho-Woo Nam Journal of Microbiology.2025; 63(2): e2409001. CrossRef
The role of Nrf2 signaling in parasitic diseases and its therapeutic potential Mohammadamin Vatankhah, Reza Panahizadeh, Ali Safari, Alireza Ziyabakhsh, Behnam Mohammadi-Ghalehbin, Narges Soozangar, Farhad Jeddi Heliyon.2024; 10(12): e32459. CrossRef
Brain –cyst-driven genes expression in Toxoplasma Gondii Tehran strain: a parasitic-immunogenicity assessment by dint of RNA-Seq Marzieh Asadi, Zahra Babaei, Ali Afgar, Mohammad Hossein Banabazi, Naser ZiaAli, Ahmad Daryani, Ehsan Aghajani, Milad Mahdavi, Mohamadreza Attari, Farzaneh Zarrinkar Veterinary Research Communications.2024; 48(4): 2563. CrossRef
BjussuLAAO-II, an l-amino acid oxidase from Bothrops jararacussu snake venom, impairs Toxoplasma gondii infection in human trophoblast cells and villous explants from the third trimester of pregnancy Thales Alves de Melo Fernandes, Samuel Cota Teixeira, Tássia Rafaela Costa, Alessandra Monteiro Rosini, Guilherme de Souza, Lorena Polloni, Bellisa de Freitas Barbosa, Marcelo José Barbosa Silva, Eloisa Amália Vieira Ferro, Veridiana de Melo Rodrigues Ávi Microbes and Infection.2023; 25(6): 105123. CrossRef
Toxoplasma gondii
inhibits the expression of autophagy-related genes through AKT-dependent inactivation of the transcription factor FOXO3a
Andres Felipe Diez, Louis-Philippe Leroux, Sophie Chagneau, Alexandra Plouffe, Mackenzie Gold, Visnu Chaparro, Maritza Jaramillo, Anita A. Koshy mBio.2023;[Epub] CrossRef
Regulation of phosphoinositide metabolism in Apicomplexan parasites Angela Arabiotorre, Vytas A. Bankaitis, Aby Grabon Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth Fei‐Fei Gao, Juan‐Hua Quan, In‐Wook Choi, Yeon‐Jae Lee, Seul‐Gi Jang, Jae‐Min Yuk, Young‐Ha Lee, Guang‐Ho Cha Journal of Cellular and Molecular Medicine.2021; 25(19): 9460. CrossRef
First
Prev
