The Role of Tim-3 on dNK Cells Dysfunction During Abnormal Pregnancy With Toxoplasma gondii Infection.
Front Cell Infect Microbiol
; 11: 587150, 2021.
Article
em En
| MEDLINE
| ID: mdl-33718261
ABSTRACT
Vertical transmission of Toxoplasma gondii (T. gondii) infection during gestation can result in severe complications such as abortion, congenital malformation, fetal teratogenesis, etc. Immune inhibitory molecule Tim-3 was discovered to be expressed on some decidual immune cells and participates in the maintenance of maternal-fetal tolerance. Dysregulation of Tim-3 expression on decidual NK (dNK) cells was observed in several cases of pregnancy complications, whereas the role of Tim-3 on dNK cells during T. gondii infection remains unclear. In the present study, T. gondii infected Tim-3-/- pregnant mice, and anti-Tim-3 neutralizing antibody treated and infected human dNK cells were successfully established to explore the role of Tim-3 in dysfunction of dNK cells during abnormal pregnancy. Our results illustrated that Tim-3-/- pregnant mice displayed more worse pregnancy outcomes with T. gondii infection compared to infected WT pregnant mice. Also, it demonstrated that Tim-3 expression on dNK cells was significantly down-regulated following T. gondii infection. Data suggested a remarkable activation of dNK cells in Tim-3-/- mice and anti-Tim-3 neutralizing antibody treated and infected groups, with higher ratios of activating receptor NKG2D to inhibitory receptor NKG2A or KIR2DL4, IFN-γ/IL-10, and increased granule production compared with that of the infected group. Mechanism analysis proved that T. gondii-induced Tim-3 down-regulation significantly activated the phosphatidylinositol-3-kinase (PI3K)-AKT and JAK-STAT signaling pathway, by which the GranzymeB, Perforin, IFN-γ, and IL-10 production were further up-regulated. Our research demonstrated that the decrease of Tim-3 on dNK cells caused by T. gondii infection further led to dNK cells function disorder, which finally contributed to the development of abnormal pregnancy outcomes.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complicações na Gravidez
/
Toxoplasma
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Toxoplasmose
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Front Cell Infect Microbiol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China