HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites

PLoS Med. 2007 May;4(5):e181. doi: 10.1371/journal.pmed.0040181.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antigens, Surface / immunology
  • Erythrocytes / immunology
  • Erythrocytes / parasitology
  • Female
  • HIV Infections / complications*
  • HIV Infections / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Macrophages / immunology
  • Malaria, Falciparum / complications*
  • Malaria, Falciparum / immunology*
  • Male
  • Monocytes / immunology
  • Muridae
  • Opsonin Proteins / immunology
  • Phagocytosis / immunology
  • Placenta / immunology
  • Placenta / parasitology
  • Placenta / virology
  • Pregnancy
  • Pregnancy Complications, Infectious* / immunology
  • Pregnancy Complications, Infectious* / parasitology
  • Pregnancy Complications, Infectious* / virology
  • Pregnancy Complications, Parasitic* / immunology
  • Pregnancy Complications, Parasitic* / parasitology
  • Pregnancy Complications, Parasitic* / virology


  • Antigens, Surface
  • Immunoglobulin G
  • Opsonin Proteins