PMID- 17431094 OWN - NLM STAT- MEDLINE DCOM- 20071105 LR - 20181201 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 21 IP - 10 DP - 2007 Aug TI - HIV-1 Nef impairs the dynamic of DC/NK crosstalk: different outcome of CD56(dim) and CD56(bright) NK cell subsets. PG - 2323-34 AB - 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. FAU - Quaranta, Maria Giovanna AU - Quaranta MG AD - Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161 Rome, Italy. FAU - Napolitano, Alfonso AU - Napolitano A FAU - Sanchez, Massimo AU - Sanchez M FAU - Giordani, Luciana AU - Giordani L FAU - Mattioli, Benedetta AU - Mattioli B FAU - Viora, Marina AU - Viora M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070412 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (CD56 Antigen) RN - 0 (Gene Products, nef) RN - 0 (Recombinant Proteins) RN - 0 (nef Gene Products, Human Immunodeficiency Virus) RN - 130068-27-8 (Interleukin-10) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Acquired Immunodeficiency Syndrome/immunology MH - CD56 Antigen/classification/drug effects/*physiology MH - Cell Division MH - Dendritic Cells/drug effects/*immunology/virology MH - Flow Cytometry MH - Gene Products, nef/*pharmacology/physiology MH - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism MH - Humans MH - Interleukin-10/metabolism MH - Killer Cells, Natural/drug effects/*immunology/virology MH - Recombinant Proteins/pharmacology MH - Virus Replication/physiology MH - nef Gene Products, Human Immunodeficiency Virus EDAT- 2007/04/14 09:00 MHDA- 2007/11/06 09:00 CRDT- 2007/04/14 09:00 PHST- 2007/04/14 09:00 [pubmed] PHST- 2007/11/06 09:00 [medline] PHST- 2007/04/14 09:00 [entrez] AID - fj.06-7883com [pii] AID - 10.1096/fj.06-7883com [doi] PST - ppublish SO - FASEB J. 2007 Aug;21(10):2323-34. doi: 10.1096/fj.06-7883com. Epub 2007 Apr 12.