Contact-dependent inhibition of HIV-1 replication in ex vivo human tonsil cultures by polymorphonuclear neutrophils

Cell Rep Med. 2021 Jun 15;2(6):100317. doi: 10.1016/j.xcrm.2021.100317.

Abstract

Polymorphonuclear neutrophils (PMNs), the most abundant white blood cells, are recruited rapidly to sites of infection to exert potent anti-microbial activity. Information regarding their role in infection with human immunodeficiency virus (HIV) is limited. Here we report that addition of PMNs to HIV-infected cultures of human tonsil tissue or peripheral blood mononuclear cells causes immediate and long-lasting suppression of HIV-1 spread and virus-induced depletion of CD4 T cells. This inhibition of HIV-1 spread strictly requires PMN contact with infected cells and is not mediated by soluble factors. 2-Photon (2PM) imaging visualized contacts of PMNs with HIV-1-infected CD4 T cells in tonsil tissue that do not result in lysis or uptake of infected cells. The anti-HIV activity of PMNs also does not involve degranulation, formation of neutrophil extracellular traps, or integrin-dependent cell communication. These results reveal that PMNs efficiently blunt HIV-1 replication in primary target cells and tissue by an unconventional mechanism.

Keywords: HIV-1 replication; antiviral activity; human tonsil explant culture; polymorphonuclear neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Cell Communication
  • Extracellular Traps
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / growth & development
  • HIV-1 / pathogenicity
  • Humans
  • Integrins / genetics
  • Integrins / immunology
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / virology
  • Neutrophils / immunology*
  • Neutrophils / virology
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology*
  • Primary Cell Culture
  • Viral Load
  • Virus Replication

Substances

  • Integrins