RESEARCH ARTICLE


Immune Suppression by Myeloid Cells in HIV Infection: New Targets for Immunotherapy



Vikram Mehraj 1, 2, Mohammad-Ali Jenabian 3, Kishanda Vyboh 1, 2, Jean-Pierre Routy1, 2, 4, *
1 Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada
2 Research Institute, McGill University Health Centre, Montreal, QC, Canada
3 Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal (UQAM), Montreal, QC, Canada
4 Division of Hematology, McGill University Health Centre, Montreal, QC, Canada


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© Mehraj et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Division of Hematology & Chronic Viral Illness Service, McGill University Health Centre, 687 Pine Avenue West, Montreal, Quebec, H3A 1A1, Canada; Tel: +1 514 843 1558; Fax: +1 514 843 1418; E-mail: jean-pierre.routy@mcgill.ca


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.

Keywords: Dendritic cells (DCs), HIV, immunotherapy, macrophages, monocytes, myeloid derived suppressor cells, neutrophils..