T granules in human platelets function in TLR9 organization and signaling.
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.
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Jonathan N
JN
Thon
Christopher G
CG
Peters
Kellie R
KR
Machlus
Rukhsana
R
Aslam
Jesse
J
Rowley
Hannah
H
Macleod
Matthew T
MT
Devine
Tobias A
TA
Fuchs
Andrew S
AS
Weyrich
John W
JW
Semple
Robert
R
Flaumenhaft
Joseph E
JE
Italiano
D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000473:pathology; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D002451:Cell Compartmentation / Q000235:genetics / Q000502:physiology; D003594:Cytoplasmic Granules / Q000502:physiology* / Q000648:ultrastructure; D015672:Erythroid Precursor Cells / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D015539:Platelet Activation / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D034061:Thrombopoiesis / Q000235:genetics / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9