Evaluating antidisease immunity to malaria and implications for vaccine design

Immunity to malaria could be categorized broadly as antiparasite or antidisease immunity. While most vaccine research efforts have focused on antiparasite immunity, the evidence from endemic populations suggest that antidisease immunity is an important component of natural immunity to malaria. The processes that mediate antidisease immunity have, however, attracted little to no attention, and most interests have been directed towards the antibody responses. This review evaluates the evidence for antidisease immunity in endemic areas and discusses the possible mechanisms responsible for it. Given the key role that inflammation plays in the pathogenesis of malaria, regulation of the inflammatory response appears to be a major mechanism for antidisease immunity in naturally exposed individuals.     

Ovarian cancer stem cells promote tumour immune privilege and invasion via CCL5 and regulatory T cells

Emerging evidence indicates a link between the increased proportion of regulatory T cells (T_regs) and reduced survival in patients who have been diagnosed with cancer. Cancer stem cells (CSCs) have been indicated to play a vital role in tumour initiation, drug resistance and recurrence. However, the relationship between T_regs and CSCs remains largely unknown. Here, we sorted out ovarian cancer stem‐like side population (SP) cells and CD133⁺ cells to investigate the influence of ovarian CSCs on T_regs. Among the various immune‐related molecules that we assessed, C‐C motif chemokine ligand 5 (CCL5) was the most elevated in ovarian CSCs relative to that in the non‐CSCs. The expression of its receptor, C‐C motif chemokine receptor 5 (CCR5), was also increased on the surface of T_regs in ovarian cancer patients. This receptor‐ligand expression profile indicated that ovarian CSCs recruit T_regs via CCL5–CCR5 interactions. We further assessed the expression of interleukin (IL)‐10 in T_regs cultured with different cancer cells. T_regs cultured in conditioned medium (CM) from ovarian CD133⁺ cells expressed a higher level of IL‐10 than T_regs cultured in CM from CD133^– cells, indicating that T_regs exert pronounced immune‐inhibitory functions in CSC‐rich environments. Furthermore, co‐culture with ovarian cancer cell lines induced the expression of matrix metalloproteinase‐9 (MMP9) in T_regs which, in turn, enhanced the degradation of the extracellular matrix and enabled the invasion of tumour cells, thereby facilitating tumour metastasis. For the first time, to our knowledge, our findings describe the relationship between ovarian CSCs and T_regs, and demonstrated that these two cell populations co‐operate to promote tumour immune tolerance and enhance tumour progression.     

Autophagy limits activation of the inflammasomes

Inflammasomes are multiprotein complexes that control the maturation and production of interleukin-1 family members and play crucial roles in host defense against pathogens. However, dysregulated activation of inflammasomes is associated with intense inflammation, leading to the development of inflammatory diseases. Therefore, inflammasomes must be activated at a proper strength to protect against infection and avoid tissue damage. Recent studies have highlighted the cross-talk between inflammasome activation and autophagy, the cellular machinery associated with the degradation of intracellular components and maintenance of cellular homeostasis. Notably, deficiencies in autophagy-related proteins induce the aberrant activation of inflammasomes, causing severe tissue damage. In contrast, autophagy inducers ameliorate symptoms of inflammasome-related diseases. In this review, we discuss recent advances in the involvement of autophagy in regulating inflammasomes activation and in the development of inflammatory diseases.     

Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH2 subsets

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The 5-time point oral glucose tolerance test as a predictor of new-onset diabetes after kidney transplantation

Aims

To evaluate the predictive power of the 5-time point oral glucose tolerance test (OGTT) for new-onset diabetes after kidney transplantation (NODAT).

Methods

We performed a retrospective study of 145 patients without diabetes who received kidney transplantations at our hospital. The 5-time point OGTT was performed before transplantation. The area under a receiver-operating characteristic curve (aROC) was used for evaluating the predictive power of 5-time point OGTT values.

Results

Seventeen patients developed NODAT within 1 year after transplantation. All postload plasma glucose (PPG) levels were higher in patients who developed NODAT than in those who did not; fasting plasma glucose levels were not different. The aROC for the area under the glucose concentration-time curve was significantly greater than that for fasting plasma glucose. Univariate and multivariate analyses showed that each PPG level was an independent risk factor for NODAT. Furthermore, patients with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) could be stratified with a 1-h plasma glucose (1h-PG) cut-off point of 8.4 mmol/L. The incidences of NODAT were 23.5%, 16.7%, 9.1%, and 0% for patients with IGT + 1h-PG ≥8.4 mmol/L,IGT + 1h-PG <8.4 mmol/L, NGT + 1h-PG ≥ 8.4 mmol/L, and NGT + 1h-PG < 8.4 mmol/L, respectively.

Conclusions

The area under the glucose concentration-time curve and each PPG concentration during the 5-time point OGTT are strong predictors of NODAT. A 1h-PG cut-off point of 8.4 mmol/L plus NGT/IGT can be used to identify patients at intermediate and high risk of developing NODAT.     

内毒素活化巨噬细胞早期和晚期基因表达的cDNA芯片分析

目的　利用 c DNA芯片技术分析内毒素活化的小鼠腹腔巨噬细胞早期和晚期基因表达 ,以更全面了解内毒素在感染、创伤反应中通过巨噬细胞介导的炎症和免疫反应。方法　以未刺激的和用 1mg/ L脂多糖 ( L PS)分别刺激 2 h(早期 )和 2 4 h(晚期 )的小鼠腹腔巨噬细胞制备 33P标记的 c DNA探针 ,并分别与小鼠 c DNA表达芯片 (含 1176个已知基因 )杂交。结果　巨噬细胞活化早期的 3倍差异表达基因为 6 9个 ,其中4 4个上调 ,2 5个下调 ;巨噬细胞活化晚期的 3倍差异表达基因中有 11个上调 ,2 6个下调 ;只有 8个基因同时出现于活化早期和晚期的差异表达基因中。许多转录因子、细胞内信号转导调节蛋白、炎症细胞因子和细胞凋亡相关基因的表达均发生了明显的调节变化。发现 BTB和 CNC同源 1( BACH1)、早期生长反应蛋白 2( EGR2 )、E4 7反应蛋白 1( EIP1)、Ngfi A结合蛋白 2 ( NAB2 )、成髓细胞白血病癌基因样蛋白 ( MYBL2 )、神经纤维癌蛋白基因 1( NF1)、睫状神经营养因子 ( CNTF)和 Sema4 A等一些以前未曾报道与 L PS诱导的巨噬细胞活化相关的基因。结论　采用 c DNA芯片技术了解内毒素诱导的巨噬细胞活化早期和晚期的综合基因表达信息 ,有助于更好地了解感染、创伤后细菌内毒素诱导的炎症免疫反应     

The glucoregulatory and antilipolytic actions of insulin in abdominal obesity with normal or impaired glucose tolerance: an in vivo and in vitro study

To evaluate the effects of obesity and impaired glucose tolerance on insulin sensitivity, we performed a euglycaemic-hyperinsulinemic clamp at about 350 pmol l-1, combined with 3H-glucose infusion, in 14 obese patients, BMI 36.5 +/- 1.2 and in 12 matched controls, BMI 23.9 +/- 0.4. Six obese patients had normal glucose tolerance (oNGT), and eight had impaired glucose tolerance (oIGT). The ability of insulin to inhibit lipolysis in isolated adipocytes was also studied. Insulin-mediated glucose utilization was more severely impaired in oIGT than in oNGT with respect to the controls (621 +/- 51 vs. 897 +/- 83 vs. 1298 +/- 55 mumol m-2 min-1, P < 0.001). Plasma glycerol was higher in oIGT than in oNGT and in the controls, both fasting (238 +/- 12 vs. 179 +/- 14 vs. 112 +/- 8 mumol l-1, P < 0.001) and during the clamp (175 +/- 21 vs. 120 +/- 12 vs. 36 +/- 6 mumol l-1, P < 0.001). The correlation between glucose utilization and the percent reduction of plasma glycerol during the clamp was significant in the study group as a whole (r = 0.809, P = 0.0001), and in each of the groups separately (oIGT: r = 0.929, P = 0.002; oNGT: r = 0.943, P = 0.036; controls: r = 0.902, P = 0.0001). Inhibition by insulin of noradrenaline-stimulated lipolysis in isolated adipocytes was more severely impaired in oIGT than in oNGT compared with the controls (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)