Toxoplasma gondii Dense Granule Antigen 1 stimulates apoptosis of monocytes through autocrine TGF-β signaling

被引：15

作者：

D'Angelillo, Anna ^{[1
]}

De Luna, Elvira ^{[1
]}

Romano, Simona ^{[1
]}

Bisogni, Rita ^{[1
]}

Buffolano, Wilma ^{[2
]}

Gargano, Nicola ^{[3
]}

Del Porto, Paola ^{[4
]}

Del Vecchio, Luigi ^{[5
]}

Petersen, Eskild ^{[6
]}

Romano, Maria Fiammetta ^{[1
]}

机构：

[1] Univ Naples Federico II, Dept Biochem & Med Biotechnol, Via S Pansini 5, I-80131 Naples, Italy

[2] Univ Naples Federico II, Dept Pediat, Perinatal Infect Unit, I-80131 Naples, Italy

[3] Kenton Srl, Kenton Labs, Rome, Italy

[4] Univ Roma La Sapienza, Dept Cellular & Dev Biol, Rome, Italy

[5] CEINGE Biotecnol Avanzate, Naples, Italy

[6] Aarhus Univ Hosp, Dept Infect Dis, DK-8000 Aarhus, Denmark

来源：

APOPTOSIS | 2011年 / 16卷 / 06期

关键词：

Toxoplasma gondii; GRA1; Apoptosis; Monocytes; TGF-beta;

D O I：

10.1007/s10495-011-0586-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Monocyte/macrophages represent the first line of defense against protozoan parasites. Different mechanisms of monocyte suppression by Toxoplasma gondii that sustain parasite invasion and persistence have been described, including apoptosis. In the present study, we investigated the effect of microbial excretory-secretory polypeptides, namely the microneme protein MIC3 and the dense granule antigen GRA1, on apoptosis of monocytes from patients with congenital toxoplasmosis and healthy individuals. We found that GRA1 but not MIC3 could induce apoptosis of monocytes, observing the effect in samples from both Toxoplasma-infected and uninfected individuals, thus ruling out involvement of mechanisms of apoptosis linked to adaptive immunity or a cellular context related to infection. Selective inhibition of TGF-beta type I receptors reversed GRA1-induced apoptosis, indicating that this apoptosis involved canonical TGF-beta signaling. By using TGF-beta-neutralizing antibodies, we showed that monocyte apoptosis required endogenous TGF-beta and that GRA1 stimulation activated TGF-beta transcription and expression in monocytes but not lymphocytes, suggesting involvement of an autocrine TGF-beta-mediated mechanism in GRA1-induced apoptosis.

引用

页码：551 / 562

页数：12

共 2 条

[1]

Toxoplasma gondii:: from animals to humans [J].