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Dendritic Cells/Natural Killer Cross-Talk: A Novel Target for Human Immunodeficiency Virus Type-1 Protease Inhibitors 1.¤ 1. 1,2 1,2 3 Maria Letizia Giardino Torchia , Elena Ciaglia , Anna Maria Masci , Laura Vitiello , Manuela Fogli , 2 4 1,5 Andrea la Sala , Domenico Mavilio , Luigi Racioppi * 1 Department of Cellular and Molecular Biology and Pathology, University of Naples ‘‘Federico II’’, Naples, Italy, 2 Laboratory of Molecular and Cellular Immunology, Department of Medical Science and Rehabilitation, IRCCS San Raffaele Pisana, Rome, Italy, 3 Section of Microbiology, Department of Experimental and Applied Medicine, University of Brescia, Brescia, Italy, 4 Laboratory of Clinical and Experimental Immunolgy, IRCCS, Istituto Clinico Humanitas, Rozzano, Milan, Italy, 5 Interdepartmental Center for Immunological Science (CISI), University of Naples ‘‘Federico II’’ Naples, Italy Abstract Background: HIV-1 Protease Inhibitors, namely PIs, originally designed to inhibit HIV-1 aspartic protease, can modulate the immune response by mechanisms largely unknown, and independent from their activity on viral replication. Here, we analyzed the ability of PIs to interfere with differentiation program of monocytes toward dendritic cell (DCs) lineage, a key process in the inflammatory response. Methodology/Principal Findings: Monocytes from healthy donors were isolated and induced to differentiate in vitro in the presence or absence of saquinavir, ritonavir, nelfinavir, indinavir or amprenavir (sqv, rtv, nlfv, idv, apv, respectively). These drugs demonstrated