Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-γ: A molecular basis for priming and synergism with bacterial lipopolysaccharide

Daniela Bosisio, Nadia Polentarutti, Marina Sironi, Sergio Bernasconi, Kensuke Miyake, Ginette R. Webb, Michael U. Martin, Alberto Mantovani, Marta Muzio

Research output: Contribution to journalArticlepeer-review

Abstract

In human monocytes and macrophages, interferon-γ (IFNγ) augmented mRNA and surface expression of toll-like receptor 4 (TLR4), a crucial component of the signaling receptor complex for bacterial lipopolysaccharide (LPS). Expression of the accessory component MD-2 and of the adapter protein MyD88 was also increased. LPS increased TLR4 mRNA levels, but concomitantly decreased its surface expression. IFNγ counteracted the LPS-induced downregulation of TLR4. IFNγ-primed monocytes showed increased responsiveness to LPS in terms of phosphorylation of the interleukin-1 receptor-associated kinase (IRAK; immediately downstream of the MyD88 adapter protein), NF-κB DNA binding activity, and, accordingly, of cytokine (tumor necrosis factor α [TNFα] and interleukin-12 [IL-12]) production. These results suggest that enhanced TLR4 expression underlies the long-known priming by IFNγ of mononuclear phagocytes for pathogen recognition and killing as well as its synergism with LPS in macrophage activation.

Original languageEnglish
Pages (from-to)3427-3431
Number of pages5
JournalBlood
Volume99
Issue number9
DOIs
Publication statusPublished - May 1 2002

ASJC Scopus subject areas

  • Hematology

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