PDF(Pubmed)
Abstract：
Adipose tissue (AT) has been highlighted as a promising reservoir of infection for viruses, bacteria and parasites. Among them is Trypanosoma cruzi, which causes Chagas disease. The recommended treatment for the disease in Brazil is Benznidazole (BZ). However, its efficacy may vary according to the stage of the disease, geographical origin, age, immune background of the host and sensitivity of the strains to the drug. In this context, AT may act as an ally for the parasite survival and persistence in the host and a barrier for BZ action. Therefore, we investigated the immunomodulation of T. cruzi-infected human AT in the presence of peripheral blood mononuclear cells (PBMC) where BZ treatment was added.
We performed indirect cultivation between T. cruzi-infected adipocytes, PBMC and the addition of BZ. After 72h of treatment, the supernatant was collected for cytokine, chemokine and adipokine assay. Infected adipocytes were removed to quantify T. cruzi DNA, and PBMC were removed for immunophenotyping.
Our findings showed elevated secretion of interleukin (IL)-6, IL-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in the AT+PBMC condition compared to the other controls. In contrast, there was a decrease in tumor necrosis factor (TNF) and IL-8/CXCL-8 in the groups with AT. We also found high adipsin secretion in PBMC+AT+T compared to the treated condition (PBMC+AT+T+BZ). Likewise, the expression of CD80+ and HLA-DR+ in CD14+ cells decreased in the presence of T. cruzi.
Thus, our findings indicate that AT promotes up-regulation of inflammatory products such as IL-6, IL-2, and MCP-1/CCL2. However, adipogenic inducers may have triggered the downregulation of TNF and IL-8/CXCL8 through the peroxisome proliferator agonist gamma (PPAR-g) or receptor expression. On the other hand, the administration of BZ only managed to reduce inflammation in the microenvironment by decreasing adipsin in the infected culture conditions. Therefore, given the findings, we can see that AT is an ally of the parasite in evading the host\'s immune response and the pharmacological action of BZ.
We performed indirect cultivation between T. cruzi-infected adipocytes, PBMC and the addition of BZ. After 72h of treatment, the supernatant was collected for cytokine, chemokine and adipokine assay. Infected adipocytes were removed to quantify T. cruzi DNA, and PBMC were removed for immunophenotyping.
Our findings showed elevated secretion of interleukin (IL)-6, IL-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in the AT+PBMC condition compared to the other controls. In contrast, there was a decrease in tumor necrosis factor (TNF) and IL-8/CXCL-8 in the groups with AT. We also found high adipsin secretion in PBMC+AT+T compared to the treated condition (PBMC+AT+T+BZ). Likewise, the expression of CD80+ and HLA-DR+ in CD14+ cells decreased in the presence of T. cruzi.
Thus, our findings indicate that AT promotes up-regulation of inflammatory products such as IL-6, IL-2, and MCP-1/CCL2. However, adipogenic inducers may have triggered the downregulation of TNF and IL-8/CXCL8 through the peroxisome proliferator agonist gamma (PPAR-g) or receptor expression. On the other hand, the administration of BZ only managed to reduce inflammation in the microenvironment by decreasing adipsin in the infected culture conditions. Therefore, given the findings, we can see that AT is an ally of the parasite in evading the host\'s immune response and the pharmacological action of BZ.
摘要：
脂肪组织（AT）已被强调为有希望的病毒感染库，细菌和寄生虫。其中包括克氏锥虫,导致查加斯病。在巴西，该疾病的推荐治疗方法是苯并硝唑（BZ）。然而,它的功效可能会根据疾病的阶段而有所不同，地理起源,年龄,宿主的免疫背景和菌株对药物的敏感性。在这种情况下，AT可能是寄生虫在宿主中存活和持久性的盟友，也是BZ作用的屏障。因此,我们研究了T.cruzi感染的人AT在外周血单核细胞（PBMC）存在下的免疫调节，其中添加了BZ治疗。
我们在克氏锥虫感染的脂肪细胞之间进行了间接培养，PBMC和BZ的添加。治疗72h后，收集上清液的细胞因子，趋化因子和脂肪因子测定。去除感染的脂肪细胞以定量T.cruziDNA，和PBMC被去除用于免疫表型分型。
我们的发现表明，与其他对照相比，AT+PBMC条件下白细胞介素（IL）-6，IL-2和单核细胞趋化蛋白-1（MCP-1/CCL2）的分泌增加。相比之下,AT组的肿瘤坏死因子（TNF）和IL-8/CXCL-8降低。我们还发现,与治疗的病症(PBMC+AT+T+BZ)相比,PBMC+AT+T中的脂肪蛋白酶分泌高。同样，在T.cruzi存在下，CD14细胞中CD80和HLA-DR的表达降低。
因此，我们的研究结果表明,AT促进IL-6,IL-2和MCP-1/CCL2等炎症产物的上调.然而,成脂诱导剂可能通过过氧化物酶体增殖物激动剂γ（PPAR-g）或受体表达触发了TNF和IL-8/CXCL8的下调。另一方面,BZ的施用仅通过在感染的培养条件下减少脂肪素而设法减少微环境中的炎症。因此,鉴于调查结果，我们可以看到，AT是一个盟友的寄生虫在逃避宿主的免疫反应和BZ的药理作用。
我们在克氏锥虫感染的脂肪细胞之间进行了间接培养，PBMC和BZ的添加。治疗72h后，收集上清液的细胞因子，趋化因子和脂肪因子测定。去除感染的脂肪细胞以定量T.cruziDNA，和PBMC被去除用于免疫表型分型。
我们的发现表明，与其他对照相比，AT+PBMC条件下白细胞介素（IL）-6，IL-2和单核细胞趋化蛋白-1（MCP-1/CCL2）的分泌增加。相比之下,AT组的肿瘤坏死因子（TNF）和IL-8/CXCL-8降低。我们还发现,与治疗的病症(PBMC+AT+T+BZ)相比,PBMC+AT+T中的脂肪蛋白酶分泌高。同样，在T.cruzi存在下，CD14细胞中CD80和HLA-DR的表达降低。
因此，我们的研究结果表明,AT促进IL-6,IL-2和MCP-1/CCL2等炎症产物的上调.然而,成脂诱导剂可能通过过氧化物酶体增殖物激动剂γ（PPAR-g）或受体表达触发了TNF和IL-8/CXCL8的下调。另一方面,BZ的施用仅通过在感染的培养条件下减少脂肪素而设法减少微环境中的炎症。因此,鉴于调查结果，我们可以看到，AT是一个盟友的寄生虫在逃避宿主的免疫反应和BZ的药理作用。
