Immunity to Placental Malaria. II. Placental Antigen–Specific Cytokine Responses Are Impaired in Human Immunodeficiency Virus–Infected Women

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Abstract
An association was demonstrated recently between elevated in vitro production of interferon (IFN)—γ by intervillous blood mononuclear cells (IVBMCs) and protection against placental malaria (PM). Because human immunodeficiency virus (HIV)—infected pregnant women have increased susceptibility to PM, loss of the IFN-γ response in these women may impair their ability to control PM. Measurement of cytokines in culture supernatants by ELISA revealed that IFN-γ responses by HIV-positive IVBMCs were impaired, especially after malarial antigen stimulation. Interleukin (IL)—4 and IL-10 responses also were reduced in HIV-positive persons, the latter more so in HIV-positive, PM-positive persons. In contrast, tumor necrosis factor—α production generally was enhanced in PM-positive and HIV-positive persons. Overall, cytokine production was reduced in HIV-positive persons with CD4 T cell counts µL, particularly in response to malarial antigen. Thus, HIV-mediated cytokine dysregulation and impairment of the protective IFN-γ response may contribute to the increased susceptibility of HIV-positive pregnant women to malaria.

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