Pseudomonas aeruginosa Infection Impairs NKG2D-Dependent NK Cell Cytotoxicity through Regulatory T-Cell Activation

Infect Immun. 2020 Nov 16;88(12):e00363-20. doi: 10.1128/IAI.00363-20. Print 2020 Nov 16.

Abstract

Natural killer (NK) cells play a key role in both antibacterial and antitumor immunity. Pseudomonas aeruginosa infection has already been reported to alter NK cell functions. We studied in vitro the effect of P. aeruginosa on NK cell cytotoxic response (CD107a membrane expression) to a lymphoma cell line. Through positive and negative cell sorting and adoptive transfer, we determined the influence of monocytes, lymphocytes, and regulatory T cells (Treg) on NK cell function during P. aeruginosa infection. We also studied the role of the activating receptor natural killer group 2D (NKG2D) in NK cell response to B221. We determined that P. aeruginosa significantly altered both cytotoxic response to B221 and NKG2D expression on NK cells in a Treg-dependent manner and that the NKG2D receptor was involved in NK cell cytotoxic response to B221. Our results also suggested that during P. aeruginosa infection, monocytes participated in Treg-mediated NK cell alteration. In conclusion, P. aeruginosa infection impairs NK cell cytotoxicity and alters antitumor immunity. These results highlight the strong interaction between bacterial infection and immunity against cancer.

Keywords: NK cells; Pseudomonas aeruginosa; cancer; immunity; infection; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic*
  • Humans
  • Killer Cells, Natural / immunology*
  • Leukocytes, Mononuclear
  • Lipopolysaccharide Receptors / metabolism
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Monocytes / immunology
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism*
  • Pseudomonas Infections / immunology*
  • Pseudomonas Infections / metabolism
  • Pseudomonas aeruginosa / immunology*
  • Signaling Lymphocytic Activation Molecule Family / metabolism
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • CD244 protein, human
  • CD3 Complex
  • KLRK1 protein, human
  • Lipopolysaccharide Receptors
  • Lysosomal-Associated Membrane Protein 1
  • NK Cell Lectin-Like Receptor Subfamily K
  • Signaling Lymphocytic Activation Molecule Family