García Killen, Escobar Gisselle, Mendoza Pablo, Beltran Caroll, Perez Claudio, Arancibia Sergio, Vernal Rolando, Rodas Paula I, Acuña-Castillo Claudio, Escobar Alejandro
Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago, Chile.
Departamento de Gastroenterología, Hospital Clínico de la Universidad de Chile, Santiago, Chile.
Mediators Inflamm. 2016;2016:1258504. doi: 10.1155/2016/1258504. Epub 2016 Oct 10.
(Ngo) has developed multiple immune evasion mechanisms involving the innate and adaptive immune responses. Recent findings have reported that Ngo reduces the IL-1 secretion of infected human monocyte-derived macrophages (MDM). Here, we investigate the role of adenosine triphosphate (ATP) in production and release of IL-1 in Ngo-infected MDM. We found that the exposure of Ngo-infected MDM to ATP increases IL-1 levels about ten times compared with unexposed Ngo-infected MDM ( < 0.01). However, we did not observe any changes in inflammasome transcriptional activation of speck-like protein containing a caspase recruitment domain (CARD) (ASC, > 0.05) and caspase-1 (CASP1, > 0.05). In addition, ATP was not able to modify caspase-1 activity in Ngo-infected MDM but was able to increase pyroptosis ( > 0.01). Notably ATP treatment defined an increase of positive staining for IL-1 with a distinctive intracellular pattern of distribution. Collectively, these data demonstrate that ATP induces IL-1 secretion by a mechanism not related to the NLRP3/ASC/caspase-1 axis and likely is acting at the level of vesicle trafficking or pore formation.
(恩戈)已经形成了多种涉及固有免疫和适应性免疫反应的免疫逃逸机制。最近的研究结果报告称,恩戈可降低被感染的人单核细胞衍生巨噬细胞(MDM)的白细胞介素-1(IL-1)分泌。在此,我们研究三磷酸腺苷(ATP)在恩戈感染的MDM中IL-1产生和释放过程中的作用。我们发现,与未暴露于ATP的恩戈感染的MDM相比,将恩戈感染的MDM暴露于ATP可使IL-1水平增加约10倍(P<0.01)。然而,我们未观察到含半胱天冬酶招募结构域(CARD)的斑点样蛋白(ASC,P>0.05)和半胱天冬酶-1(CASP1,P>0.05)的炎性小体转录激活有任何变化。此外,ATP无法改变恩戈感染的MDM中的半胱天冬酶-1活性,但能够增加细胞焦亡(P<0.01)。值得注意的是,ATP处理确定了IL-1阳性染色增加,且具有独特的细胞内分布模式。总体而言,这些数据表明,ATP通过一种与NLRP3/ASC/半胱天冬酶-1轴无关的机制诱导IL-1分泌,并且可能在囊泡运输或孔形成水平发挥作用。