TY - JOUR
T1 - Depletion of Intracellular Glutamine Pools Triggers Toxoplasma gondii Stage Conversion in Human Glutamatergic Neurons
AU - Bando, Hironori
AU - Fukuda, Yasuhiro
AU - Watanabe, Nina
AU - Olawale, Jeje Temitope
AU - Kato, Kentaro
N1 - Funding Information:
This study was funded by grants-in-aid for Scientific Research (B:17H03913) Young Scientists (19K16628), and Young Scientists (B) (17K15677) from the Ministry of Education, Culture, Science, Sports, and Technology (MEXT) of Japan, and by a Livestock Promotional Subsidy from the Japan Racing Association, the Uehara Memorial Foundation (J200002710), and The Morinaga Foundation for Health & Nutrition (AV602061).
Publisher Copyright:
Copyright © 2022 Bando, Fukuda, Watanabe, Olawale and Kato.
PY - 2022/1/13
Y1 - 2022/1/13
N2 - Toxoplasma gondii chronically infects the brain as latent cysts containing bradyzoites and causes various effects in the host. Recently, the molecular mechanisms of cyst formation in the mouse brain have been elucidated, but those in the human brain remain largely unknown. Here, we show that abnormal glutamine metabolism caused by both interferon-γ (IFN-γ) stimulation and T. gondii infection induce cyst formation in human neuroblastoma cells regardless of the anti-T. gondii host factor nitric oxide (NO) level or Indoleamine 2,3-dioxygenase-1 (IDO1) expression. IFN-γ stimulation promoted intracellular glutamine degradation in human neuronal cells. Additionally, T. gondii infection inhibited the mRNA expression of the host glutamine transporters SLC38A1 and SLC38A2. These dual effects led to glutamine starvation and triggered T. gondii stage conversion in human neuronal cells. Furthermore, these mechanisms are conserved in human iPSC-derived glutamatergic neurons. Taken together, our data suggest that glutamine starvation in host cells is an important trigger of T. gondii stage conversion in human neurons.
AB - Toxoplasma gondii chronically infects the brain as latent cysts containing bradyzoites and causes various effects in the host. Recently, the molecular mechanisms of cyst formation in the mouse brain have been elucidated, but those in the human brain remain largely unknown. Here, we show that abnormal glutamine metabolism caused by both interferon-γ (IFN-γ) stimulation and T. gondii infection induce cyst formation in human neuroblastoma cells regardless of the anti-T. gondii host factor nitric oxide (NO) level or Indoleamine 2,3-dioxygenase-1 (IDO1) expression. IFN-γ stimulation promoted intracellular glutamine degradation in human neuronal cells. Additionally, T. gondii infection inhibited the mRNA expression of the host glutamine transporters SLC38A1 and SLC38A2. These dual effects led to glutamine starvation and triggered T. gondii stage conversion in human neuronal cells. Furthermore, these mechanisms are conserved in human iPSC-derived glutamatergic neurons. Taken together, our data suggest that glutamine starvation in host cells is an important trigger of T. gondii stage conversion in human neurons.
KW - IFN-γ
KW - Toxoplasma gondii
KW - bradyzoite
KW - human
KW - iPSC-derived glutamatergic neurons
UR - http://www.scopus.com/inward/record.url?scp=85123785133&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123785133&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2021.788303
DO - 10.3389/fcimb.2021.788303
M3 - Article
C2 - 35096641
AN - SCOPUS:85123785133
SN - 2235-2988
VL - 11
JO - Frontiers in cellular and infection microbiology
JF - Frontiers in cellular and infection microbiology
M1 - 788303
ER -
