來自Toronto大學的科學家最近發(fā)現(xiàn)孕婦對抗瘧疾以及HIV抵消這一過程的內部機制,。這一發(fā)現(xiàn)將有助于尋找?guī)椭懠彩⑿械貐^(qū)孕婦對抗這一疾病的疫苗,。
瘧疾是一種蚊子傳播的疾病，每年它導致超過100萬人死亡,。瘧疾最常感染兒童和孕婦,，特別是首次懷孕的婦女,。這每年造成大約400000例嚴重的瘧疾,，并導致200000例嬰兒死亡。最近科學家發(fā)現(xiàn)HIV將進一步加重孕期瘧疾（PAM）,，因此了解這些疾病并且找到治療方案是很關鍵的,。
直到最近孕婦對抗瘧疾以及HIV破壞這一過程的機制還尚不清楚，但是發(fā)表在《PLoS Medicine》上的一篇文章指出了這些病毒如何影響孕婦的免疫反應,。PAM發(fā)生時,，紅細胞將被瘧原蟲感染，它們會聚集在胎盤上,，從而導致母親和胎兒都受到破壞,。首次懷孕的婦女尤其危險，而再次懷孕的婦女有一定的免疫能力,。但是HIV將使這些婦女失去免疫力,，從而變得和首次懷孕者一樣危險。
為了找到HIV影響PAM的原因,，文章第一作者Kevin Kain和他的小組收集了來自肯尼亞的婦女的樣本,，肯尼亞是一個瘧疾盛行的地區(qū)?？茖W家發(fā)現(xiàn),，一種特殊的抗體使得婦女能優(yōu)先清除存在于胎盤上的瘧原蟲。但感染了HIV的婦女將失去這一抗體,，從而變得對PAM易感,。
以上發(fā)現(xiàn)將幫助研發(fā)針對PAM的疫苗，Kain說：“這還只是尋找治療手段的第一步,，我們期望能利用這一發(fā)現(xiàn)制造出更有效的各種瘧疾疫苗,。”
??原文鏈接：http://www.physorg.com/news99672565.html
??劉樂譯自：physorg.com
原始出處:
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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