TY - JOUR
T1 - Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infection
AU - Xiao, Jianchun
AU - Li, Ye
AU - Rowley, Treva
AU - Huang, Jing
AU - Yolken, Robert H.
AU - Viscidi, Raphael P.
N1 - Funding Information:
This work was supported by the Stanley Medical Research Institute (SMRI).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Toxoplasma gondii can infect the host brain and trigger neuroinflammation. Such neuroinflammation might persist for years if the infection is not resolved, resulting in harmful outcomes for the brain. We have previously demonstrated the efficacy of immunotherapy targeting the programmed cell death protein 1 (PD-1) pathway on clearance of Toxoplasma tissue cysts. We aimed to test whether parasite clearance would lead to the resolution of neuroinflammation in infected brains. We established chronic Toxoplasma infection in BALB/c mice using the cyst-forming Prugniaud strain. Mice then received αPD-L1 or isotype control antibodies. After completion of the therapy, mice were euthanized six weeks later. The number of brain tissue cysts, Toxoplasma-specific CD8 + T cell proliferation and IFN-γ secretion, serum cytokine and chemokine levels, and CNS inflammation were measured. In αPD-L1-treated mice, we observed reduced brain tissue cysts, increased spleen weight, elevated IFN-γ production by antigen-specific CD8 + T cells, and a general increase in multiple serum cytokines and chemokines. Importantly, αPD-L1-treated mice displayed attenuation of meningeal lymphocytes, reactive astrocytes, and C1q expression. The reduction in inflammation-related proteins is correlated with reduced parasite burden. These results suggest that promoting systemic immunity results in parasite clearance, which in turn alleviates neuroinflammation. Our study may have implications for some brain infections where neuroinflammation is a critical component.
AB - Toxoplasma gondii can infect the host brain and trigger neuroinflammation. Such neuroinflammation might persist for years if the infection is not resolved, resulting in harmful outcomes for the brain. We have previously demonstrated the efficacy of immunotherapy targeting the programmed cell death protein 1 (PD-1) pathway on clearance of Toxoplasma tissue cysts. We aimed to test whether parasite clearance would lead to the resolution of neuroinflammation in infected brains. We established chronic Toxoplasma infection in BALB/c mice using the cyst-forming Prugniaud strain. Mice then received αPD-L1 or isotype control antibodies. After completion of the therapy, mice were euthanized six weeks later. The number of brain tissue cysts, Toxoplasma-specific CD8 + T cell proliferation and IFN-γ secretion, serum cytokine and chemokine levels, and CNS inflammation were measured. In αPD-L1-treated mice, we observed reduced brain tissue cysts, increased spleen weight, elevated IFN-γ production by antigen-specific CD8 + T cells, and a general increase in multiple serum cytokines and chemokines. Importantly, αPD-L1-treated mice displayed attenuation of meningeal lymphocytes, reactive astrocytes, and C1q expression. The reduction in inflammation-related proteins is correlated with reduced parasite burden. These results suggest that promoting systemic immunity results in parasite clearance, which in turn alleviates neuroinflammation. Our study may have implications for some brain infections where neuroinflammation is a critical component.
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U2 - 10.1038/s41598-023-28322-8
DO - 10.1038/s41598-023-28322-8
M3 - Article
C2 - 36690687
AN - SCOPUS:85146790500
SN - 2045-2322
VL - 13
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 1288
ER -