Division of Surgical Research, Brown University/Rhode Island Hospital, Providence, Rhode Island, USA.
Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA.
Surg Infect (Larchmt). 2021 May;22(4):400-408. doi: 10.1089/sur.2020.233. Epub 2020 Sep 30.
Sepsis-related mortality is driven by immune dysfunction. A bidirectional micro-organism-immune cell cross talks exists. Gut -T-cell crosstalk maintains innate immune cell/pathogen homeostasis. Commensal gut spp. suppress inflammation and induce gut tolerance. Probiotics are administered to restore immune microbiome homeostasis. Individual microbial components have an immunomodulatory effect. However, probiotic therapies for sepsis-induced immune disruptions are rarely tailored to specific immune responses. Thus, we ask the question as to how components of the intestinal microbiome, often found in probiotic therapies, affect lymphocyte phenotypic profile? T-lymphocytes were cultured with either monomicrobial or polymicrobial combinations. Microbes used were , , or . Cytokines, measured by enzyme-linked immunosorbent assay (ELISA)-included interleukin (IL)-6, IL-10, IL-22, and IL-33. Flow cytometry was used for T-cell phenotyping for program-death receptor-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA). T-cell DNA was extracted to assess global epigenetic changes. For translation, IL-33 was measured from surgical intensive care unit (ICU) patients with sepsis with either monomicrobial or polymicrobial infection. consistently induced IL-22 and IL-33. induced IL-33 only under polymicrobial (pB) conditions. Within surgical ICU patients, IL-33 levels were higher in polymicrobial versus monomicrobial patients. PD-1 expression was lowest with either monomicrobial or predominant polymicrobial context. Conversely exposure induced a distinct PD-1 subpopulation. B- and T-lymphocyte attenuator-positive expression did not differ after individual microbes. Among polymicrobial conditions, predominant (pB) and predominant (pL) increased BTLA expression. DNA methylation was most increased in response to in monomicrobial and in response to in polymicrobial conditions. Unique microbe/lymphocyte interactions occur. induced a T-cell phenotype consistent with potential long-term immune recovery. This work begins to discover how varying microbes may induce unique functional and phenotypic T-lymphocyte responses.
与脓毒症相关的死亡率是由免疫功能障碍驱动的。微生物-免疫细胞之间存在双向交流。肠道 - T 细胞相互作用维持固有免疫细胞/病原体的平衡。共生肠道 spp. 抑制炎症并诱导肠道耐受。益生菌用于恢复免疫微生物组的平衡。个体微生物成分具有免疫调节作用。然而，用于脓毒症引起的免疫紊乱的益生菌治疗很少针对特定的免疫反应进行调整。因此，我们提出了这样一个问题，即肠道微生物组的成分，通常存在于益生菌治疗中，如何影响淋巴细胞表型谱？ T 淋巴细胞与单微生物或多微生物组合培养。使用的微生物包括 、 、 。通过酶联免疫吸附试验 (ELISA) 测量细胞因子，包括白细胞介素 (IL)-6、IL-10、IL-22 和 IL-33。流式细胞术用于 T 细胞表型分析程序性死亡受体-1 (PD-1) 和 B 和 T 淋巴细胞衰减器 (BTLA)。提取 T 细胞 DNA 以评估全基因组表观遗传变化。为了进行翻译，从脓毒症合并单微生物或多微生物感染的外科重症监护病房 (ICU) 患者中测量了 IL-33。 一致地诱导了 IL-22 和 IL-33。 仅在多微生物 (pB) 条件下诱导 IL-33。在外科 ICU 患者中，多微生物患者的 IL-33 水平高于单微生物患者。在单微生物 或 主要多微生物环境中，PD-1 表达最低。 暴露诱导了一个独特的 PD-1 亚群。在单个微生物后，B 和 T 淋巴细胞衰减器阳性表达没有差异。在多微生物条件下， 主要 (pB) 和 主要 (pL) 增加了 BTLA 表达。在单微生物和多微生物条件下， 响应时 DNA 甲基化增加最多。存在独特的微生物/淋巴细胞相互作用。 诱导与潜在长期免疫恢复一致的 T 细胞表型。这项工作开始发现不同的微生物如何诱导独特的功能性和表型 T 淋巴细胞反应。
