Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules.

Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules.
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DOI:
10.1080/22221751.2020.1818632
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发表时间:
2020-12
影响因子:
13.2
通讯作者:
Santos-Preciado JI
Santos-Preciado JI
中科院分区:
医学2区
文献类型:
--
作者:
Rosales-Reyes R;Garza-Villafuerte P;Vences-Vences D;Aubert DF;Aca-Teutle R;Ortiz-Navarrete VF;Bonifaz LC;Carrero-Sánchez JC;Olivos-García A;Valvano MA;Santos-Preciado JI

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伯克霍尔德菌是囊性纤维化和慢性肉芽肿病患者的一种新出现的机会性病原体。膜结合液泡(BcCV)内巨噬细胞的细胞内存活延缓了酸化和溶酶体的成熟,这是cenocepacia感染的一个标志。胞内结核杆菌诱导炎症反应,通过细菌脱酰胺酶的分泌导致pyrin炎性体的激活,导致巨噬细胞热亡。然而,被感染的巨噬细胞如何或是否可以加工和呈递新梢芽孢杆菌抗原来激活t细胞尚未被探索。被吞噬的细菌蛋白抗原在内体晚期主要组织相容性II类复合体(MHC)隔室(MIIC)中被切割成小肽。在这里,我们证明了bccv和MIICs具有重叠的特征,并且干扰素γ激活的巨噬细胞感染了cenocepacia B.可以加工细菌抗原,通过II类MHC分子呈递给CD4+ t细胞,通过I类MHC分子呈递给CD8+ t细胞。被感染的巨噬细胞也将处理过的细菌肽释放到细胞外培养基中,稳定旁观者细胞的空I类MHC分子。综上所述,我们得出结论,bccv获得了MIIC特征,支持了巨噬细胞感染新绿芽胞杆菌有助于建立针对病原体的适应性免疫反应的观点。
Burkholderia cenocepacia is an emerging opportunistic pathogen for people with cystic fibrosis and chronic granulomatous disease. Intracellular survival in macrophages within a membrane-bound vacuole (BcCV) that delays acidification and maturation into lysosomes is a hallmark of B. cenocepacia infection. Intracellular B. cenocepacia induce an inflammatory response leading to macrophage cell death by pyroptosis through the secretion of a bacterial deamidase that results in the activation of the pyrin inflammasome. However, how or whether infected macrophages can process and present B. cenocepacia antigens to activate T-cells has not been explored. Engulfed bacterial protein antigens are cleaved into small peptides in the late endosomal major histocompatibility class II complex (MHC) compartment (MIIC). Here, we demonstrate that BcCVs and MIICs have overlapping features and that interferon-gamma-activated macrophages infected with B. cenocepacia can process bacterial antigens for presentation by class II MHC molecules to CD4+ T-cells and by class I MHC molecules to CD8+ T-cells. Infected macrophages also release processed bacterial peptides into the extracellular medium, stabilizing empty class I MHC molecules of bystander cells. Together, we conclude that BcCVs acquire MIIC characteristics, supporting the notion that macrophages infected with B. cenocepacia contribute to establishing an adaptive immune response against the pathogen.
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发表时间: 2003-09-25
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