HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites

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.