来自Toronto大学的科学家最近发现孕妇对抗疟疾以及HIV抵消这一过程的内部机制。这一发现将有助于寻找帮助疟疾盛行地区孕妇对抗这一疾病的疫苗。
疟疾是一种蚊子传播的疾病，每年它导致超过100万人死亡。疟疾最常感染儿童和孕妇，特别是首次怀孕的妇女。这每年造成大约400000例严重的疟疾，并导致200000例婴儿死亡。最近科学家发现HIV将进一步加重孕期疟疾（PAM），因此了解这些疾病并且找到治疗方案是很关键的。
直到最近孕妇对抗疟疾以及HIV破坏这一过程的机制还尚不清楚，但是发表在《PLoS Medicine》上的一篇文章指出了这些病毒如何影响孕妇的免疫反应。PAM发生时，红细胞将被疟原虫感染，它们会聚集在胎盘上，从而导致母亲和胎儿都受到破坏。首次怀孕的妇女尤其危险，而再次怀孕的妇女有一定的免疫能力。但是HIV将使这些妇女失去免疫力，从而变得和首次怀孕者一样危险。
为了找到HIV影响PAM的原因，文章第一作者Kevin Kain和他的小组收集了来自肯尼亚的妇女的样本，肯尼亚是一个疟疾盛行的地区。科学家发现，一种特殊的抗体使得妇女能优先清除存在于胎盘上的疟原虫。但感染了HIV的妇女将失去这一抗体，从而变得对PAM易感。
以上发现将帮助研发针对PAM的疫苗，Kain说：“这还只是寻找治疗手段的第一步，我们期望能利用这一发现制造出更有效的各种疟疾疫苗。”
??原文链接：http://www.physorg.com/news99672565.html
??刘乐译自：physorg.com
原始出处:
PLoS Medicine
Received: August 18, 2006; Accepted: March 30, 2007; Published: May 29, 2007
HIV Impairs Opsonic Phagocytic Clearance of Pregnancy-Associated Malaria Parasites
Jessica Keen1, Lena Serghides1,2,3, Kodjo Ayi1, Samir N. Patel1, John Ayisi4, Anne van Eijk4, Richard Steketee5, Venkatachalam Udhayakumar5, Kevin C. Kain1,2,3*
1 Faculty of Medicine, University of Toronto, Toronto, Canada, 2 McLaughlin-Rotman Centre, McLaughlin Center for Molecular Medicine, University of Toronto, Toronto, Canada, 3 University Health Network, Toronto, Canada, 4 Center for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya, 5 Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
Background
Primigravid (PG) women are at risk for pregnancy-associated malaria (PAM). Multigravid (MG) women acquire protection against PAM; however, HIV infection impairs this protective response. Protection against PAM is associated with the production of IgG specific for variant surface antigens (VSA-PAM) expressed by chondroitin sulfate A (CSA)-adhering parasitized erythrocytes (PEs). We hypothesized that VSA-PAM-specific IgG confers protection by promoting opsonic phagocytosis of PAM isolates and that HIV infection impairs this response.
Methods and Findings
We assessed the ability of VSA-PAM-specific IgG to promote opsonic phagocytosis of CSA-adhering PEs and the impact of HIV infection on this process. Opsonic phagocytosis assays were performed using the CSA-adherent parasite line CS2 and human and murine macrophages. CS2 PEs were opsonized with plasma or purified IgG subclasses from HIV-negative or HIV-infected PG and MG Kenyan women or sympatric men. Levels of IgG subclasses specific for VSA-PAM were compared in HIV-negative and HIV-infected women by flow cytometry. Plasma from HIV-negative MG women, but not PG women or men, promoted the opsonic phagocytosis of CSA-binding PEs (p < 0.001). This function depended on VSA-PAM-specific plasma IgG1 and IgG3. HIV-infected MG women had significantly lower plasma opsonizing activity (median phagocytic index 46 [interquartile range (IQR) 18–195] versus 251 [IQR 93–397], p = 0.006) and levels of VSA-PAM-specific IgG1 (mean fluorescence intensity [MFI] 13 [IQR 11–20] versus 30 [IQR 23–41], p < 0.001) and IgG3 (MFI 17 [IQR 14–23] versus 28 [IQR 23–37], p < 0.001) than their HIV-negative MG counterparts.
Conclusions
Opsonic phagocytosis may represent a novel correlate of protection against PAM. HIV infection may increase the susceptibility of multigravid women to PAM by impairing this clearance mechanism.
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