title: Host Immune Responses in HIV-1 Infection: The Emerging Pathogenic Role of Siglecs and Their Clinical Correlates.
abstract: A better understanding of the mechanisms employed by HIV-1 to escape immune responses still represents one of the major tasks required for the development of novel therapeutic approaches targeting a disease still lacking a definitive cure. Host innate immune responses against HIV-1 are key in the early phases of the infection as they could prevent the development and the establishment of two hallmarks of the infection: chronic inflammation and viral reservoirs. Sialic acid-binding immunoglobulin-like lectins (Siglecs) belong to a family of transmembrane proteins able to dampen host immune responses and set appropriate immune activation thresholds upon ligation with their natural ligands, the sialylated carbohydrates. This immune-modulatory function is also targeted by many pathogens that have evolved to express sialic acids on their surface in order to escape host immune responses. HIV-1 envelope glycoprotein 120 (gp120) is extensively covered by carbohydrates playing active roles in life cycle of the virus. Indeed, besides forming a protecting shield from antibody recognition, this coat of N-linked glycans interferes with the folding of viral glycoproteins and enhances virus infectivity. In particular, the sialic acid residues present on gp120 can bind Siglec-7 on natural killer and monocytes/macrophages and Siglec-1 on monocytes/macrophages and dendritic cells. The interactions between these two members of the Siglec family and the sialylated glycans present on HIV-1 envelope either induce or increase HIV-1 entry in conventional and unconventional target cells, thus contributing to viral dissemination and disease progression. In this review, we address the impact of Siglecs in the pathogenesis of HIV-1 infection and discuss how they could be employed as clinic and therapeutic targets.
authors.affiliation: Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Italy; Istituto di Ricerca Genetica e Biomedica, UOS di Milano, Consiglio Nazionale delle Ricerche (UOS/IRGB/CNR), Rozzano, Italy.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mikulak
authors.affiliation: Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center , Rozzano , Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Di Vito
authors.affiliation: Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center , Rozzano , Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zaghi
authors.affiliation: Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Italy; Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Milan, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Mavilio
keywords: NK cells; dendritic cells; host-pathogen interactions; monocytes/macrophages