title: Activation of human natural killer cells by the novel innate immune modulator recombinant Eimeria antigen.
abstract: The safe and effective activation of the innate and adaptive immune systems are crucial in the implementation of immunotherapeutic modalities for the prevention and treatment of human diseases. Eimeria antigen (EA) and its recombinantly expressed analog (rEA) are extremely effective activators of innate immunity in mice. The effects of rEA in the mouse are primarily mediated through the TLR11/12 MyD88 signaling system. Human cells lack functional TLR11 and TLR12, suggesting that rEA would not be effective in providing beneficial immune activation in humans. In the current report we provide definitive evidence that the treatment of human peripheral blood mononuclear cell (PBMC) cultures with rEA significantly up regulates CD69, CD107, NKG2D levels on NK cells. Furthermore, rEA stimulates human NK cell effector functions including increasing intracellular levels of IFNγ and Granzyme B. These responses are positively correlated with an improved capacity of rEA stimulated human PBMCs to kill NK cell-sensitive human K562 tumor cells. Importantly, rEA-triggered innate immune responses was not associated with increased pro-inflammatory cytokines and chemokines production. These data confirm a previously unidentified role for rEA in human immune cell activation, and suggests the utilization of rEA in immunotherapies against a variety of infectious diseases and cancers.
authors: Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, USA.
authors: Charles F
authors: CF
authors: Aylsworth
authors: Yasser A
authors: YA
authors: Aldhamen
authors: Sergey S
authors: SS
authors: Seregin
authors: Sarah
authors: S
authors: Godbehere
authors: Andrea
authors: A
authors: Amalfitano
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000953:Antigens, Protozoan / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004539:Eimeria / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D010641:Phenotype; D000091402:Prohibitins; D011994:Recombinant Proteins / Q000276:immunology* / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000819:agonists; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051200:Toll-Like Receptor 8 / Q000819:agonists
chemical_list: D015703:Antigens, CD; D000953:Antigens, Protozoan; D016207:Cytokines; D055654:NK Cell Lectin-Like Receptor Subfamily C; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011994:Recombinant Proteins; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8
keywords: ADCC; CFSE; Carboxyfluorescein Succinimidyl Ester; EA; Eimeria antigen; FITC; LDH; MFI; PI; antibody dependent cell-mediated cytotoxicity; fluorescein isothiocyanate; lactate dehydrogenase; mean fluorescence intensity; propidium iodide; rEA; recombinant EA