PMID- 25313083
OWN - NLM
STAT- MEDLINE
DCOM- 20150417
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 111
IP  - 43
DP  - 2014 Oct 28
TI  - TLR-dependent phagosome tubulation in dendritic cells promotes phagosome 
      cross-talk to optimize MHC-II antigen presentation.
PG  - 15508-13
LID - 10.1073/pnas.1412998111 [doi]
AB  - Dendritic cells (DCs) phagocytose large particles like bacteria at sites of 
      infection and progressively degrade them within maturing phagosomes. Phagosomes 
      in DCs are also signaling platforms for pattern recognition receptors, such as 
      Toll-like receptors (TLRs), and sites for assembly of cargo-derived peptides with 
      major histocompatibility complex class II (MHC-II) molecules. Although TLR 
      signaling from phagosomes stimulates presentation of phagocytosed antigens, the 
      mechanisms underlying this enhancement and the cell surface delivery of 
      MHC-II-peptide complexes from phagosomes are not known. We show that in DCs, 
      maturing phagosomes extend numerous long tubules several hours after 
      phagocytosis. Tubule formation requires an intact microtubule and actin 
      cytoskeleton and MyD88-dependent phagosomal TLR signaling, but not phagolysosome 
      formation or extensive proteolysis. In contrast to the tubules that emerge from 
      endolysosomes after uptake of soluble ligands and TLR stimulation, the late-onset 
      phagosomal tubules are not essential for delivery of phagosome-derived 
      MHC-II-peptide complexes to the plasma membrane. Rather, tubulation promotes 
      MHC-II presentation by enabling maximal cargo transfer among phagosomes that bear 
      a TLR signature. Our data show that phagosomal tubules in DCs are functionally 
      distinct from those that emerge from lysosomes and are unique adaptations of the 
      phagocytic machinery that facilitate cargo exchange and antigen presentation 
      among TLR-signaling phagosomes.
FAU - Mantegazza, Adriana R
AU  - Mantegazza AR
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, PA 19104; Department of Physiology and.
FAU - Zajac, Allison L
AU  - Zajac AL
AD  - Department of Physiology and Cell and Molecular Biology Graduate Group, Perelman 
      School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; and.
FAU - Twelvetrees, Alison
AU  - Twelvetrees A
AD  - Department of Physiology and.
FAU - Holzbaur, Erika L F
AU  - Holzbaur EL
AD  - Department of Physiology and.
FAU - Amigorena, Sebastian
AU  - Amigorena S
AD  - Section de Recherche, Institut Curie and INSERM U932, 75005 Paris, France.
FAU - Marks, Michael S
AU  - Marks MS
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, PA 19104; Department of Physiology and 
      marksm@mail.med.upenn.edu.
LA  - eng
GR  - P01 GM087253/GM/NIGMS NIH HHS/United States
GR  - R01 EY015625/EY/NEI NIH HHS/United States
GR  - R21 AI092398/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141013
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Actins)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Peptides)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Antigen Presentation/*immunology
MH  - Dendritic Cells/*immunology
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Lipopolysaccharides
MH  - Lysosomes/metabolism
MH  - Mice, Inbred C57BL
MH  - Microtubules/metabolism
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - Peptides/metabolism
MH  - Phagosomes/*immunology
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/metabolism
MH  - Toll-Like Receptors/*metabolism
PMC - PMC4217451
OTO - NOTNLM
OT  - Toll-like receptors
OT  - inflammation
OT  - major histocompatibility complex
OT  - microtubules
OT  - phagocytosis
COIS- The authors declare no conflict of interest.
EDAT- 2014/10/15 06:00
MHDA- 2015/04/18 06:00
PMCR- 2015/04/28
CRDT- 2014/10/15 06:00
PHST- 2014/10/15 06:00 [entrez]
PHST- 2014/10/15 06:00 [pubmed]
PHST- 2015/04/18 06:00 [medline]
PHST- 2015/04/28 00:00 [pmc-release]
AID - 1412998111 [pii]
AID - 201412998 [pii]
AID - 10.1073/pnas.1412998111 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15508-13. doi: 
      10.1073/pnas.1412998111. Epub 2014 Oct 13.