HIV Impairs Opsonic Phagocytic Clearance of Pregnancy-Associated Malaria Parasites Export

@article{citeulike:1368873, abstract = {BackgroundPrimigravid (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 FindingsWe 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 \&\#60; 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 \&\#91;interquartile range (IQR) 18\&\#8211;195\&\#93; versus 251 \&\#91;IQR 93\&\#8211;397\&\#93;, p \&\#61; 0.006) and levels of VSA-PAM-specific IgG1 (mean fluorescence intensity \&\#91;MFI\&\#93; 13 \&\#91;IQR 11\&\#8211;20\&\#93; versus 30 \&\#91;IQR 23\&\#8211;41\&\#93;, p \&\#60; 0.001) and IgG3 (MFI 17 \&\#91;IQR 14\&\#8211;23\&\#93; versus 28 \&\#91;IQR 23\&\#8211;37\&\#93;, p \&\#60; 0.001) than their HIV-negative MG counterparts.ConclusionsOpsonic 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.}, author = {Keen, Jessica and Serghides, Lena and Ayi, Kodjo and Patel, Samir N. and Ayisi, John and van Eijk, Anne and Steketee, Richard and Udhayakumar, Venkatachalam and Kain, Kevin C.}, citeulike-article-id = {1368873}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pmed.0040181}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17535103}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17535103}, day = {1}, doi = {10.1371/journal.pmed.0040181}, journal = {PLoS Medicine}, keywords = {coinfection, hiv, immunology, journal-club, malaria, pathogenesis, pregnancy-malaria}, month = {May}, number = {5}, pages = {e181+}, posted-at = {2007-06-06 20:27:24}, priority = {4}, title = {HIV Impairs Opsonic Phagocytic Clearance of Pregnancy-Associated Malaria Parasites}, url = {http://dx.doi.org/10.1371/journal.pmed.0040181}, volume = {4}, year = {2007} }

TY - JOUR ID - citeulike:1368873 L3 - citeulike-article-id:1368873 N2 - BackgroundPrimigravid (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 FindingsWe 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.ConclusionsOpsonic 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. IS - 5 JF - PLoS Medicine TI - HIV Impairs Opsonic Phagocytic Clearance of Pregnancy-Associated Malaria Parasites VL - 4 SP - e181 KW - coinfection KW - hiv KW - immunology KW - journal-club KW - malaria KW - pathogenesis KW - pregnancy-malaria AU - Keen, Jessica AU - Serghides, Lena AU - Ayi, Kodjo AU - Patel, Samir AU - Ayisi, John AU - van Eijk, Anne AU - Steketee, Richard AU - Udhayakumar, Venkatachalam AU - Kain, Kevin PY - 2007/05/01/ UR - http://dx.doi.org/10.1371/journal.pmed.0040181 ER -