title: Natural killer cell and macrophage cooperation in MyD88-dependent innate responses to Plasmodium falciparum.
abstract: IFN-gamma secretion by natural killer (NK) cells is pivotal to several tumor and viral immune responses, during which NK and dendritic cells cooperation is required. We show here that macrophages are mandatory for NK cell IFN-gamma secretion in response to erythrocytes infected with Plasmodium falciparum (Pf), a causative agent of human malaria. In addition, direct sensing of Pf infection by NK cells induces their production of the proinflammatory chemokine CXCL8, without triggering their granule-mediated cytolytic programs. Despite their reported role in Pf recognition, Toll-like receptor (TLR) 2, TLR9, and TLR11 are individually dispensable for NK cell activation induced by Pf-infected erythrocytes. However, IL-18R expression on NK cells, IL-18 production by macrophages, and MyD88 on both cell types are essential components of this previously undescribed pathway of NK cell activation in response to a parasite infection.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université delaMéditerranée, 13288 Marseille, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Baratin
authors.forename: Sophie
authors.initials: S
authors.lastname: Roetynck
authors.forename: Catherine
authors.initials: C
authors.lastname: Lépolard
authors.forename: Christine
authors.initials: C
authors.lastname: Falk
authors.forename: Serge
authors.initials: S
authors.lastname: Sawadogo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Jean-Gérard
authors.initials: JG
authors.lastname: Tiraby
authors.forename: Lena
authors.initials: L
authors.lastname: Alexopoulou
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: Jürg
authors.initials: J
authors.lastname: Gysin
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Sophie
authors.initials: S
authors.lastname: Ugolini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000818:Animals; D019743:Chemokines, CXC / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88; D010963:Plasmodium falciparum / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019743:Chemokines, CXC; D020382:Interleukin-18; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; D007371:Interferon-gamma