Tim-3 downregulation by Toxoplasma gondii infection contributes to decidual dendritic cell dysfunction.
Parasit Vectors
; 15(1): 393, 2022 Oct 27.
Article
en En
| MEDLINE
| ID: mdl-36303229
ABSTRACT
BACKGROUND:
Women in early pregnancy infected by Toxoplasma gondii may have severe adverse pregnancy outcomes, such as spontaneous abortion and fetal malformation. The inhibitory molecule T cell immunoglobulin and mucin domain 3 (Tim-3) is highly expressed on decidual dendritic cells (dDCs) and plays an important role in maintaining immune tolerance. However, whether T. gondii infection can cause dDC dysfunction by influencing the expression of Tim-3 and further participate in adverse pregnancy outcomes is still unclear.METHODS:
An abnormal pregnancy model in Tim-3-deficient mice and primary human dDCs treated with Tim-3 neutralizing antibodies were used to examine the effect of Tim-3 expression on dDC dysfunction after T. gondii infection.RESULTS:
Following T. gondii infection, the expression of Tim-3 on dDCs was downregulated, those of the pro-inflammatory functional molecules CD80, CD86, MHC-II, tumor necrosis factor-α (TNF-α), and interleukin-12 (IL-12) were increased, while those of the tolerant molecules indoleamine 2,3-dioxygenase (IDO) and interleukin-10 (IL-10) were significantly reduced. Tim-3 downregulation by T. gondii infection was closely associated with an increase in proinflammatory molecules and a decrease in tolerant molecules, which further resulted in dDC dysfunction. Moreover, the changes in Tim-3 induced by T. gondii infection further reduced the secretion of the cytokine IL-10 via the SRC-signal transducer and activator of transcription 3 (STAT3) pathway, which ultimately contributed to abnormal pregnancy outcomes.CONCLUSIONS:
Toxoplasma gondii infection can significantly downregulate the expression of Tim-3 and cause the aberrant expression of functional molecules in dDCs. This leads to dDC dysfunction, which can ultimately contribute to abnormal pregnancy outcomes. Further, the expression of the anti-inflammatory molecule IL-10 was significantly decreased by Tim-3 downregulation, which was mediated by the SRC-STAT3 signaling pathway in dDCs after T. gondii infection.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
3_ND
Problema de salud:
2_enfermedades_transmissibles
/
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Células Dendríticas
/
Toxoplasmosis
/
Receptor 2 Celular del Virus de la Hepatitis A
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
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Humans
/
Pregnancy
Idioma:
En
Revista:
Parasit Vectors
Año:
2022
Tipo del documento:
Article