title: Polyfunctional natural killer cells with a low activation profile in response to Toll-like receptor 3 activation in HIV-1-exposed seronegative subjects.
abstract: Natural killer (NK) cells are the main mediator of the cytotoxic response in innate immunity and may be involved in resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Toll-like receptor (TLR) signalling is crucial for NK cell activation. Here, we investigated the polyfunctional NK cell response to TLR3 activation in serodiscordant couples. ESN subjects showed increased IFN-γ and CD107a expression in both NK subsets, CD56brightand CD56dimcells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners. TLR3-induced expression of IFN-γ, TNF and CD107a by polyfunctional CD56brightNK cells was more pronounced in ESN individuals than that in healthy controls. Activated NK cells, as determined by CD38 expression, were increased only in the HIV-1-infected partners, with reduced IFN-γ and CD107a expression. Moreover, CD38+NK cells of the HIV-1-infected partners were associated with increased expression of inhibitory molecules, such as NKG2A, PD-1 and Tim-3, while NK cells from ESN subjects showed decreased NKG2A expression. Altogether, these findings indicate that NK cells of ESN individuals were highly responsive to TLR3 activation and had a polyfunctional NK cell phenotype, while the impaired TLR3 response in HIV-1-infected partners was associated with an inhibitory/exhaustion NK cell phenotype.
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Josenilson F
authors.initials: JF
authors.lastname: Lima
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Luanda M S
authors.initials: LMS
authors.lastname: Oliveira
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Nátalli Z
authors.initials: NZ
authors.lastname: Pereira
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Alberto J S
authors.initials: AJS
authors.lastname: Duarte
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. marisato@usp.br.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Sato
mesh_terms: D015415:Biomarkers; D019002:CD56 Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D010641:Phenotype; D051196:Toll-Like Receptor 3 / Q000819:agonists*
chemical_list: D015415:Biomarkers; D019002:CD56 Antigen; D016207:Cytokines; D051196:Toll-Like Receptor 3; D019041:L-Selectin