Subramaniam Krishanthi S, Skinner Jeff, Ivan Emil, Mutimura Eugene, Kim Ryung S, Feintuch Catherine M, Portugal Silvia, Anastos Kathryn, Crompton Peter D, Daily Johanna P
Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, NIAID/NIH, Bethesda, Maryland, United States of America.
PLoS One. 2015 Apr 30;10(4):e0124412. doi: 10.1371/journal.pone.0124412. eCollection 2015.
HIV infected individuals in malaria endemic areas experience more frequent and severe malaria episodes compared to non HIV infected. This clinical observation has been linked to a deficiency in antibody responses to Plasmodium falciparum antigens; however, prior studies have only focused on the antibody response to <0.5% of P. falciparum proteins. To obtain a broader and less-biased view of the effect of HIV on antibody responses to malaria we compared antibody profiles of HIV positive (HIV+) and negative (HIV-) Rwandan adults with symptomatic malaria using a microarray containing 824 P. falciparum proteins. We also investigated the cellular basis of the antibody response in the two groups by analyzing B and T cell subsets by flow cytometry. Although HIV malaria co-infected individuals generated antibodies to a large number of P. falciparum antigens, including potential vaccine candidates, the breadth and magnitude of their response was reduced compared to HIV- individuals. HIV malaria co-infection was also associated with a higher percentage of atypical memory B cells (MBC) (CD19+CD10-CD21-CD27-) compared to malaria infection alone. Among HIV+ individuals the CD4+ T cell count and HIV viral load only partially explained variability in the breadth of P. falciparum-specific antibody responses. Taken together, these data indicate that HIV malaria co-infection is associated with an expansion of atypical MBCs and a diminished antibody response to a diverse array of P. falciparum antigens, thus offering mechanistic insight into the higher risk of malaria in HIV+ individuals.
与未感染艾滋病毒的人相比，疟疾流行地区的艾滋病毒感染者经历疟疾发作的频率更高且病情更严重。这一临床观察结果与针对恶性疟原虫抗原的抗体反应缺陷有关；然而，先前的研究仅关注了对不到0.5%的恶性疟原虫蛋白质的抗体反应。为了更全面、更客观地了解艾滋病毒对疟疾抗体反应的影响，我们使用包含824种恶性疟原虫蛋白质的微阵列，比较了患有症状性疟疾的卢旺达成年艾滋病毒阳性（HIV+）和阴性（HIV-）个体的抗体谱。我们还通过流式细胞术分析B细胞和T细胞亚群，研究了两组中抗体反应的细胞基础。尽管艾滋病毒与疟疾合并感染的个体产生了针对大量恶性疟原虫抗原（包括潜在疫苗候选抗原）的抗体，但其反应的广度和强度与未感染艾滋病毒的个体相比有所降低。与单纯疟疾感染相比，艾滋病毒与疟疾合并感染还与更高比例的非典型记忆B细胞（MBC）（CD19+CD10-CD21-CD27-）相关。在艾滋病毒阳性个体中，CD4+T细胞计数和艾滋病毒病毒载量仅部分解释了恶性疟原虫特异性抗体反应广度的变异性。综上所述，这些数据表明，艾滋病毒与疟疾合并感染与非典型MBC的扩增以及对多种恶性疟原虫抗原的抗体反应减弱有关，从而为艾滋病毒阳性个体患疟疾风险更高提供了机制性见解。
