Cytokines TNFα, IFNγ and IL-2 Are Responsible for Signal Transmission from the Innate Immunity Protein Tag7 (PGLYRP1) to Cytotoxic Effector Lymphocytes

Cells. 2020 Dec 4;9(12):2602. doi: 10.3390/cells9122602.

Abstract

Studies on the mechanisms of activation of cytotoxic lymphocyte subpopulations are an important research direction in modern immunology. This study provides a detailed analysis of the effect of Tag7 (PGRP-S, PGLYRP1) on the development of lymphocyte subpopulations cytotoxic against MHC-negative tumor cells in a pool of peripheral blood mononuclear cells (PBMCs). The results show that Tag7 can bind to the TREM-1 receptor on the surfaces of monocytes, thereby triggering the expression of mRNA TNFα and IFNγ. The appearance of these cytokines in conditioned medium leads to IL-2 cytokine secretion by CD3+CD4+ lymphocytes. In turn, IL-2 facilitates unspecific activation of three cytotoxic cell subpopulations in the PBMC pool: NK (CD16+CD56+), CD3+CD4+ and CD3+CD8+. These subpopulations appear after a certain period of incubation with Tag7 and show toxicity against tumor cells.

Keywords: PGLYRP1; TREM-1; cancer immunology; cytokines; monocytes; programmed cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Apoptosis
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / cytology*
  • Cell Separation
  • Cytokines / metabolism*
  • Cytotoxicity, Immunologic
  • Humans
  • Immunity, Innate
  • Interferon-gamma / metabolism*
  • Interleukin-2 / metabolism*
  • K562 Cells
  • Killer Cells, Natural / immunology
  • Leukocytes, Mononuclear / cytology
  • Lymphocytes / cytology
  • Monocytes / metabolism
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Anti-Bacterial Agents
  • CD3 Complex
  • Cytokines
  • IFNG protein, human
  • IL2 protein, human
  • Interleukin-2
  • PGLYRP1 protein, human
  • RNA, Messenger
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma