School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom ; Malawi Liverpool Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
PLoS One. 2013 Nov 4;8(11):e78592. doi: 10.1371/journal.pone.0078592. eCollection 2013.
Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV-infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19(+) CD27(+) IgM(+) IgD(+)) depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease.
肺炎球菌病与艾滋病毒流行国家成年人的发病率和死亡率特别高有关。我们之前的研究结果表明,来自同一人群的艾滋病毒感染儿童存在 B 细胞缺陷,这促使我们全面描述了来自马拉维的轻度症状艾滋病毒感染成年人的 B 细胞亚群,并研究了针对肺炎球菌的同种型转换 IgG 记忆 B 细胞免疫反应。我们发现,与垂直获得性艾滋病毒感染的马拉维儿童相似,这些成年人的水平获得性艾滋病毒感染与 IgM 记忆 B 细胞(CD19(+) CD27(+) IgM(+) IgD(+))耗竭、B 细胞激活和针对一系列肺炎球菌蛋白的特异性 IgG B 细胞记忆受损有关。我们的数据表明,艾滋病毒感染会影响 T 细胞非依赖性和 T 细胞依赖性 B 细胞成熟,可能导致对细胞外病原体(如肺炎球菌)的体液反应受损,从而使该人群易患侵袭性疾病。