Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll-like receptors 2 and 4

Michela Spadaro, Monica Montone, Maddalena Arigoni, Daniela Cantarella, Guido Forni, Federica Pericle, Steve Pascolo, Raffaele A. Calogero, Federica Cavallo

Research output: Contribution to journalArticlepeer-review

Abstract

Lactoferrin, a key component of innate immunity, is a cationic monomeric 80-kDa glycoprotein of the transferrin superfamily. Recombinant human lactoferrin, known as talactoferrin (TLF), induces a distinct functional maturation program in human dendritic cells (DCs) derived from peripheral blood monocytes. However, the receptors and molecular mechanisms involved in this induction have not been fully determined. By exploiting genome-wide transcription profiling of immature DCs, TNF-α- and IL-1β-matured DCs (m-DCs), and TLF-matured DCs (TLF-DCs), we have detected a set of transcripts specific for m-DCs and one specific for TLF-DCs. Functional network reconstruction highlighted, as expected, the association of m-DC maturation with IL-1β, TNF-α, and NF-κB, whereas TLF-DC maturation was associated with ERK and NF-κB. This involvement of ERK and NF-κB transduction factors suggests direct involvement of Toll-like receptors (TLRs) in TLF-induced maturation. We have used MyD88 inhibition and siRNA silencing TLRs on human DCs and mouse TLR-2-knockout cells, to show that TLF triggers the maturation of both human and mouse DCs through TLR-2 and TLR-4.

Original languageEnglish
Pages (from-to)416-429
Number of pages14
JournalFASEB Journal
Volume28
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • Alarmins
  • Pattern recognition receptors

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

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