Mass Cytometry Reveals the Immaturity of Circulating Neutrophils during SIV Infection

J Innate Immun. 2020;12(2):170-181. doi: 10.1159/000499841. Epub 2019 Jun 21.

Abstract

The infected host fails to eradicate HIV-1, despite significant control of viral replication by combinational antiretroviral therapy. Here, we assessed the impact of HIV infection on immune-cell compartments in a SIVmac251 nonhuman primate infection model, which allowed the choice of contamination route, time of infection, and treatment follow-up. We performed high-throughput multiparameter single-cell phenotyping by mass cytometry to obtain a global vision of the immune system in blood and bone marrow. Circulating polymorphonuclear neutrophils (PMNs) with impaired phagocytosis had altered surface expression of CD62L and CD11b during early chronic infection. The initiation of combinational antiretroviral treatment during primary infection did not restore PMN function. The maturation state of PMNs was highly altered during late chronic SIV infection, showing a primarily immature phenotype. Our results provide new insights into PMN involvement in the pathogenesis of HIV infection and may play a role in the establishment and maintenance of chronic immune activation.

Keywords: AIDS; Antiretroviral treatment; Mass cytometry; Neutrophils; Nonhuman primate; Phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Flow Cytometry*
  • Macaca fascicularis
  • Male
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Simian Acquired Immunodeficiency Syndrome / blood
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus / immunology*
  • Simian Immunodeficiency Virus / metabolism