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IFN- and IL-10 Mediate Parasite-Specific Immune Responses of Cord Blood Cells Induced by Pregnancy-Associated Plasmodium falciparum Malaria¹

Kim Brustoski^*,, Ulrike Möller, Martin Kramer, Annika Petelski, Stephan Brenner, Dupeh R. Palmer, Martina Bongartz^*, Peter G. Kremsner^*,, Adrian J. F. Luty^*, and Urszula Krzych^2,

^* Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon; and Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910

Available evidence suggests that immune cells from neonates born to mothers with placental Plasmodium falciparum (Pf) infection are sensitized to parasite Ag in utero but have reduced ability to generate protective Th1 responses. In this study, we detected Pf Ag-specific IFN-⁺ T cells in cord blood from human neonates whose mothers had received treatment for malaria or who had active placental Pf infection at delivery, with responses being significantly reduced in the latter group. Active placental malaria at delivery was also associated with reduced expression of monocyte MHC class I and II in vivo and following short term in vitro coculture with Pf Ag compared with levels seen in neonates whose mothers had received treatment during pregnancy. Given that APC activation and Th1 responses are driven in part by IFN- and down-regulated by IL-10, we examined the role of these cytokines in modulating the Pf Ag-specific immune responses in cord blood samples. Exogenous recombinant human IFN- and neutralizing anti-human IL-10 enhanced T cell IFN- production, whereas recombinant human IFN- also restored MHC class I and II expression on monocytes from cord blood mononuclear cells cocultured with Pf Ag. Accordingly, active placental malaria at delivery was associated with increased frequencies of Pf Ag-specific IL-10⁺CD4⁺ T cells in cord blood mononuclear cell cultures from these neonates. Generation and maintenance of IL-10⁺ T cells in utero may thus contribute to suppression of APC function and Pf Ag-induced Th1 responses in newborns born to mothers with placental malaria at delivery, which may increase susceptibility to infection later in life.

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