title: Memory-like IFN-γ response by NK cells following malaria infection reveals the crucial role of T cells in NK cell activation by P. falciparum.
abstract: NK cells are rapid IFN-γ responders to Plasmodium falciparum-infected erythrocytes (PfRBC) in vitro and are involved in controlling early parasitaemia in murine models, yet little is known about their contribution to immune responses following malaria infection in humans. Here, we studied the dynamics of and requirements for in vitro NK responses to PfRBC in malaria-naïve volunteers undergoing a single experimental malaria infection under highly controlled circumstances, and in naturally exposed individuals. NK-specific IFN-γ responses to PfRBC following exposure resembled an immunological recall pattern and were tightly correlated with T-cell responses. However, although PBMC depleted of CD56(+) cells retained 20-55% of their total IFN-γ response to PfRBC, depletion of CD3(+) cells completely abrogated the ability of remaining PBMC, including NK cells, to produce IFN-γ. Although NK responses to PfRBC were partially dependent on endogenous IL-2 signaling and could be augmented by exogenous IL-2 in whole PBMC populations, this factor alone was insufficient to rescue NK responses in the absence of T cells. Thus, NK cells make a significant contribution to total IFN-γ production in response to PfRBC as a consequence of their dependency on (memory) T-cell help, with likely positive implications for malaria vaccine development.
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Matthew B B
authors.initials: MB
authors.lastname: McCall
authors.forename: Meta
authors.initials: M
authors.lastname: Roestenberg
authors.forename: Ivo
authors.initials: I
authors.lastname: Ploemen
authors.forename: Anne
authors.initials: A
authors.lastname: Teirlinck
authors.forename: Joost
authors.initials: J
authors.lastname: Hopman
authors.forename: Quirijn
authors.initials: Q
authors.lastname: de Mast
authors.forename: Amagana
authors.initials: A
authors.lastname: Dolo
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Adrian
authors.initials: A
authors.lastname: Luty
authors.forename: André J A M
authors.initials: AJ
authors.lastname: van der Ven
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
mesh_terms: D017252:CD3 Complex / Q000096:biosynthesis; D019002:CD56 Antigen / Q000096:biosynthesis; D002450:Cell Communication; D002478:Cells, Cultured; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D018189:Immunomagnetic Separation; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D008213:Lymphocyte Activation; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D017780:Malaria Vaccines; D007371:Interferon-gamma