title: Immune Suppression by Myeloid Cells in HIV Infection: New Targets for Immunotherapy.
abstract: Over thirty years of extensive research has not yet solved the complexity of HIV pathogenesis leading to a continued need for a successful cure. Recent immunotherapy-based approaches are aimed at controlling the infection by reverting immune dysfunction. Comparatively less appreciated than the role of T cells in the context of HIV infection, the myeloid cells including macrophages monocytes, dendritic cells (DCs) and neutrophils contribute significantly to immune dysfunction. Host restriction factors are cellular proteins expressed in these cells which are circumvented by HIV. Guided by the recent literature, the role of myeloid cells in HIV infection will be discussed highlighting potential targets for immunotherapy. HIV infection, which is mainly characterized by CD4 T cell dysfunction, also manifests in a vicious cycle of events comprising of inflammation and immune activation. Targeting the interaction of programmed death-1 (PD-1), an important regulator of T cell function; with PD-L1 expressed mainly on myeloid cells could bring promising results. Macrophage functional polarization from pro-inflammatory M1 to anti-inflammatory M2 and vice versa has significant implications in viral pathogenesis. Neutrophils, recently discovered low density granular cells, myeloid derived suppressor cells (MDSCs) and yolk sac macrophages provide new avenues of research on HIV pathogenesis and persistence. Recent evidence has also shown significant implications of neutrophil extracellular traps (NETs), antimicrobial peptides and opsonizing antibodies. Further studies aimed to understand and modify myeloid cell restriction mechanisms have the potential to contribute in the future development of more effective anti-HIV interventions that may pave the way to viral eradication.
authors.affiliation: Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada ; Research Institute, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Vikram
authors.initials: V
authors.lastname: Mehraj
authors.affiliation: Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal (UQAM), Montreal, QC, Canada.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.affiliation: Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada ; Research Institute, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Kishanda
authors.initials: K
authors.lastname: Vyboh
authors.affiliation: Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada ; Research Institute, McGill University Health Centre, Montreal, QC, Canada ; Division of Hematology, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
keywords: Dendritic cells (DCs); HIV; immunotherapy; macrophages; monocytes; myeloid derived suppressor cells; neutrophils.