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FASEB J ; 21(10): 2323-34, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17431094

RESUMO

Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immunity and play a critical role in the first phase of host defense against infection. Interactions between DCs and NK cells have been demonstrated in a variety of settings, with evidence emerging of complex bidirectional crosstalk between the two cell types. The accessory HIV-1 Nef protein is a crucial determinant for viral replication and pathogenesis. We previously demonstrated that Nef, hijacking DC functional activity, subverts the DC arm of immune response to escape the adaptive immune attack. Here, we monitor the effect of Nef on the outcome of the innate immune response, focusing on the impact of Nef on DC/NK crosstalk. We demonstrate that Nef up-regulates the ability of DCs to stimulate the immunoregulatory NK cells (CD56(bright)) as assessed by the activated phenotype, up-regulation of their proliferative response and INF-gamma release. On the other hand, Nef-pulsed DCs inhibit cytotoxic NK cells (CD56(dim)), as assessed by the reduced HLA-DR surface expression, reduced proliferation and cytotoxic activity. Moreover, in the presence of Nef-pulsed DCs, we found a significant up-regulation of TNF-alpha secretion and a significant reduction of IL-10, GM-CSF, MIP-1alpha and RANTES secretion. Our findings suggest that the Nef-induced dysregulation in the DC/NK cell crosstalk may represent a potential mechanism through which HIV escapes innate immune surveillance.


Assuntos
Antígeno CD56/fisiologia , Células Dendríticas/imunologia , Produtos do Gene nef/farmacologia , Células Matadoras Naturais/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Antígeno CD56/classificação , Antígeno CD56/efeitos dos fármacos , Divisão Celular , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/virologia , Citometria de Fluxo , Produtos do Gene nef/fisiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Interleucina-10/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/virologia , Proteínas Recombinantes/farmacologia , Replicação Viral/fisiologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana
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