Heterogeneous human NK cell responses to Plasmodium falciparum-infected erythrocytes

DS Korbel, Kirsty C. Newman, CR Almeida, DM Davis, EM Riley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Human NK cells can respond rapidly to Plasmodium falciparum-infected RBC (iRBC) to produce IFN-gamma. In this study, we have examined the heterogeneity of this response among malaria-naive blood donors. Cells from all donors become partially activated (up-regulating CD69, perforin, and granzyme) upon exposure to iRBC but cells from only a subset of donors become fully activated (additionally up-regulating CD25, IFN-gamma, and surface expression of lysosomal-associated membrane protein 1 (LAMP1)). Although both CD56(dim) and CD56(bright) NK cell populations can express IFN-gamma in response to iRBC, CD25 and LAMP-1 are up-regulated only by CD56(dim) NK cells and CD69 is up-regulated to a greater extent in this subset; by contrast, perforin and granzyme A are preferentially up-regulated by CD56(bright) NK cells. NK cells expressing IFN-gamma in response to iRBC always coexpress CD69 and CD25 but rarely LAMP-1, suggesting that individual NK cells respond to iRBC either by IFN-gamma production or cytotoxicity. Furthermore, physical contact with iRBC can, in a proportion of donors, lead to NK cell cytoskeletal reorganization suggestive of functional interactions between the cells. These observations imply that individuals may vary in their ability to mount an innate immune response to malaria infection with obvious implications for disease resistance or susceptibility.

Original languageEnglish
Pages (from-to)7466-7473
Number of pages8
JournalJournal of Immunology
Volume175
Issue number11
DOIs
Publication statusPublished - 1 Dec 2005

Keywords

  • NATURAL-KILLER-CELLS
  • INNATE IMMUNITY
  • GAMMA-INTERFERON
  • CYTOKINE PRODUCTION
  • AFRICAN CHILDREN
  • DENDRITIC CELLS
  • MALARIA
  • ACTIVATION
  • RECEPTOR
  • CHABAUDI

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