Activation of cytokine-producing and antitumor activities of natural killer cells and macrophages by engagement of Toll-like and NOD-like receptors

Fu Qiu, Amudhan Maniar, Marco Quevedo Diaz, Andrei Chapoval, Andrei E. Medvedev

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Macrophages and natural killer (NK) cells are important antitumor effectors by virtue of their ability to produce cytokines, chemokines and interferons (IFNs) and to mediate tumor cytotoxicity. Little is known about the impact of Toll-like receptor (TLR) and nucleotide binding and oligomerization domain (NOD)-like receptor (NLR) pathways on NK cell functions, and the role of TLRs and NLRs in macrophage activation is incompletely understood. In this study, we examined the capacities of expressed TLRs and NLRs to elicit cytokine production in human NK cells and THP1 macrophages, and to activate NK cytotoxicity against the squamous cell carcinoma of head and neck cell line Tu167 and erythroleukemia K562 cells. We found that NK cells express high levels of NOD2, NLRP3, TLR3, TLR7, and TLR9, while NOD1 was expressed at low levels. All tested NLR and TLR agonists potentiated NK cytotoxicity against Tu167 cells, whereas only poly (I:C) increased NK cytotoxicity against K562 cells. Poly (I:C) and Escherichia coli RNA markedly up-regulated TNF-α and IFN-γ expression in the NK92 cell line and human CD56 +CD3 - primary NK cells. High levels of NOD2, TLR7 and TLR9 proteins were observed in human THP1 cells, followed by TLR3, NOD1, and NLRP3. Stimulation of NLRP3 with E. coli RNA led to the highest induction of TNF-α, IL-6, IL-12p40, RANTES and IFN-β, whereas TLR7, TLR3, TLR9, NOD1 and NOD2 agonists had lower effects. Our data reveal involvement of TLRs and NLRs in potentiation of antitumor cytotoxicity and cytokine-producing activities of human NK cells and macrophages.

Original languageEnglish (US)
Pages (from-to)375-387
Number of pages13
JournalInnate Immunity
Volume17
Issue number4
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Fingerprint

Natural Killer Cells
Macrophages
Cytokines
Interferons
K562 Cells
Toll-Like Receptors
Interleukin-12 Subunit p40
Toll-Like Receptor 9
RNA
Escherichia coli
Cell Line
Chemokine CCL5
Leukemia, Erythroblastic, Acute
Macrophage Activation
Chemokines
Human Activities
NLR Proteins
Interleukin-6
Nucleotides
Neoplasms

Keywords

  • cell activation
  • Innate immunity
  • NK cells/macrophages
  • signal transduction
  • Toll-like receptors

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Immunology
  • Microbiology
  • Infectious Diseases

Cite this

Activation of cytokine-producing and antitumor activities of natural killer cells and macrophages by engagement of Toll-like and NOD-like receptors. / Qiu, Fu; Maniar, Amudhan; Quevedo Diaz, Marco; Chapoval, Andrei; Medvedev, Andrei E.

In: Innate Immunity, Vol. 17, No. 4, 01.08.2011, p. 375-387.

Research output: Contribution to journalArticle

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