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Infection and Immunity, June 2005, p. 3462-3470, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3462-3470.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Distinct Th1- and Th2-Type Prenatal Cytokine Responses to Plasmodium falciparum Erythrocyte Invasion Ligands

Indu Malhotra,1 Peter Mungai,1 Eric Muchiri,2 John Ouma,3 Shobhona Sharma,4 James W. Kazura,1 and Christopher L. King1,5*

Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio,1 Division of Vector Borne Diseases, Nairobi, Kenya,2 Maseno University, Maseno, Kenya,3 Tata Institute of Fundamental Research, Mumbai, India,4 Department of Veterans’ Affairs Medical Center, Cleveland, Ohio5

Received 24 November 2004/ Returned for modification 7 January 2005/ Accepted 28 January 2005

Prenatal immunity to Plasmodium falciparum merozoite proteins involved in erythrocyte invasion may contribute to the partial protection against malaria that is acquired during infancy in areas of stable malaria transmission. We examined newborn and maternal cytokine and antibody responses to merozoite surface protein-1 (MSP-1), ribosomal phosphoprotein P0 (PfP0), and region II of erythrocyte binding antigen-175 (EBA-175) in infant-mother pairs in Kenya. Overall, 82 of 167 (50%), 106 of 176 (60%), and 38 of 84 (45%) cord blood lymphocytes (CBL) from newborns produced one or more cytokines in response to MSP-1, PfP0, and EBA-175, respectively. Newborns of primigravid and/or malaria-infected women were more likely to have antigen-responsive CBL than were newborns of multigravid and/or uninfected women at delivery. Newborn cytokine responses did not match those of their mothers and fell into three distinct categories, Th1 (21 of 55 CBL donors produced only gamma interferon and/or interleukin 2 [IL-2]), Th2 (21 of 55 produced only IL-5 and/or IL-13), and mixed Th1/Th2 (13 of 55). Newborns produced more IL-10 than adults. High and low levels of cord blood IL-12 p70 production induced by anti-CD40 activation were associated with malaria-specific Th1 and Th2 responses, respectively. Antigen-responsive CBL in some newborns were detected only after depletion of IL-10-secreting CD8 cells with enrichment for CD4 cells. These data indicate that prenatal sensitization to blood-stage Plasmodium falciparum occurs frequently in areas where malaria is holoendemic. Modulation of this immunity, possibly by maternal parity and malaria, may affect the acquisition of protective immunity against malaria during infancy.

* Corresponding author. Mailing address: Center for Global Health and Diseases, Case Western Reserve University, 2103 Cornell Rd., WRC Room 4132, Cleveland, OH 44106-7286. Phone: (216) 368-4817. Fax: (216) 368-4825. E-mail: christopher.king{at}case.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, June 2005, p. 3462-3470, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3462-3470.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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