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.


RESULTS
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.
Keen
Jessica
J
Faculty of Medicine, University of Toronto, Toronto, Canada.
Serghides
Lena
L
Ayi
Kodjo
K
Patel
Samir N
SN
Ayisi
John
J
van Eijk
Anne
A
Steketee
Richard
R
Udhayakumar
Venkatachalam
V
Kain
Kevin C
KC
D000293:Adolescent; D000328:Adult; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008264:Macrophages / Q000276:immunology; D016778:Malaria, Falciparum / Q000150:complications* / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology; D009115:Muridae; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D010920:Placenta / Q000276:immunology / Q000469:parasitology / Q000821:virology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000469:parasitology / Q000821:virology; D015597:Pregnancy Complications, Parasitic / Q000276:immunology / Q000469:parasitology / Q000821:virology
D000954:Antigens, Surface; D007074:Immunoglobulin G; D009895:Opsonin Proteins