T细胞反应与急性类鼻疽病患者的生存情况相关。
T-Cell Responses Are Associated with Survival in Acute Melioidosis Patients.
作者信息
Jenjaroen Kemajittra, Chumseng Suchintana, Sumonwiriya Manutsanun, Ariyaprasert Pitchayanant, Chantratita Narisara, Sunyakumthorn Piyanate, Hongsuwan Maliwan, Wuthiekanun Vanaporn, Fletcher Helen A, Teparrukkul Prapit, Limmathurotsakul Direk, Day Nicholas P J, Dunachie Susanna J
机构信息
Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
出版信息
PLoS Negl Trop Dis. 2015 Oct 23;9(10):e0004152. doi: 10.1371/journal.pntd.0004152. eCollection 2015 Oct.
BACKGROUND
Melioidosis is an increasingly recognised cause of sepsis and death across South East Asia and Northern Australia, caused by the bacterium Burkholderia pseudomallei. Risk factors include diabetes, alcoholism and renal disease, and a vaccine targeting at-risk populations is urgently required. A better understanding of the protective immune response in naturally infected patients is essential for vaccine design.
METHODS
We conducted a longitudinal clinical and immunological study of 200 patients with melioidosis on admission, 12 weeks (n = 113) and 52 weeks (n = 65) later. Responses to whole killed B. pseudomallei were measured in peripheral blood mononuclear cells (PBMC) by interferon-gamma (IFN-γ) ELIspot assay and flow cytometry and compared to those of control subjects in the region with diabetes (n = 45) and without diabetes (n = 43).
RESULTS
We demonstrated strong CD4+ and CD8+ responses to B. pseudomallei during acute disease, 12 weeks and 52 weeks later. 28-day mortality was 26% for melioidosis patients, and B. pseudomallei-specific cellular responses in fatal cases (mean 98 IFN-γ cells per million PBMC) were significantly lower than those in the survivors (mean 142 IFN-γ cells per million PBMC) in a multivariable logistic regression model (P = 0.01). A J-shaped curve association between circulating neutrophil count and mortality was seen with an optimal count of 4000 to 8000 neutrophils/μl. Melioidosis patients with known diabetes had poor diabetic control (median glycated haemoglobin HbA1c 10.2%, interquartile range 9.2-13.1) and showed a stunted B. pseudomallei-specific cellular response during acute illness compared to those without diabetes.
CONCLUSIONS
The results demonstrate the role of both CD4+ and CD8+ T-cells in protection against melioidosis, and an interaction between diabetes and cellular responses. This supports development of vaccine strategies that induce strong T-cell responses for the control of intracellular pathogens such as B. pseudomallei.
背景
类鼻疽是由伪马鼻疽伯克霍尔德菌引起的一种败血症和死亡原因，在东南亚和澳大利亚北部越来越受到关注。危险因素包括糖尿病、酗酒和肾脏疾病，迫切需要一种针对高危人群的疫苗。更好地了解自然感染患者的保护性免疫反应对于疫苗设计至关重要。
方法
我们对200例类鼻疽患者进行了一项纵向临床和免疫学研究，分别在入院时、12周（n = 113）和52周（n = 65）后进行。通过干扰素-γ（IFN-γ）酶联免疫斑点试验和流式细胞术检测外周血单核细胞（PBMC）对全灭活伪马鼻疽伯克霍尔德菌的反应，并与该地区患有糖尿病（n = 45）和未患糖尿病（n = 43）的对照受试者进行比较。
结果
我们证明在急性疾病期间、12周和52周后，患者对伪马鼻疽伯克霍尔德菌有强烈的CD4 +和CD8 +反应。类鼻疽患者的28天死亡率为26%，在多变量逻辑回归模型中，致命病例中伪马鼻疽伯克霍尔德菌特异性细胞反应（每百万PBMC中平均98个IFN-γ细胞）显著低于幸存者（每百万PBMC中平均142个IFN-γ细胞）（P = 0.01）。循环中性粒细胞计数与死亡率之间呈J形曲线关联，最佳计数为4000至8000个中性粒细胞/μl。已知患有糖尿病的类鼻疽患者糖尿病控制不佳（糖化血红蛋白HbA1c中位数为10.2%，四分位间距为9.2 - 13.1），与未患糖尿病的患者相比，在急性疾病期间伪马鼻疽伯克霍尔德菌特异性细胞反应发育不良。
结论
结果证明了CD4 +和CD8 + T细胞在预防类鼻疽中的作用，以及糖尿病与细胞反应之间存在相互作用。这支持开发诱导强烈T细胞反应以控制细胞内病原体（如伪马鼻疽伯克霍尔德菌）的疫苗策略。
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