T granules in human platelets function in TLR9 organization and signaling

Research output: Contribution to journalArticle

Abstract

Human and murine platelets (PLTs) variably express toll-like receptors (TLRs), which link the innate and adaptive immune responses during infectious inflammation and atherosclerotic vascular disease. In this paper, we show that the TLR9 transcript is specifically up-regulated during pro-PLT production and is distributed to a novel electron-dense tubular system-related compartment we have named the T granule. TLR9 colocalizes with protein disulfide isomerase and is associated with either VAMP 7 or VAMP 8, which regulates its distribution in PLTs on contact activation (spreading). Preincubation of PLTs with type IV collagen specifically increased TLR9 and CD62P surface expression and augmented oligodeoxynucleotide (ODN) sequestration and PLT clumping upon addition of bacterial/viral ODNs. Collectively, this paper (a) tracks TLR9 to a new intracellular compartment in PLTs and (b) describes a novel mechanism of TLR9 organization and signaling in human PLTs.

Details

Authors
  • Jonathan N Thon
  • Christopher G Peters
  • Kellie R Machlus
  • Rukhsana Aslam
  • Jesse Rowley
  • Hannah Macleod
  • Matthew T Devine
  • Tobias A Fuchs
  • Andrew S Weyrich
  • John W Semple
  • Robert Flaumenhaft
  • Joseph E Italiano
External organisations
  • Saint Michael's Hospital
Research areas and keywords

Keywords

  • Animals, Atherosclerosis, Blood Platelets, Cell Compartmentation, Cytoplasmic Granules, Erythroid Precursor Cells, Humans, Mice, Platelet Activation, Signal Transduction, Thrombopoiesis, Toll-Like Receptor 9, Up-Regulation, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)561-74
Number of pages14
JournalJournal of Cell Biology
Volume198
Issue number4
Publication statusPublished - 2012 Aug 20
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes