PMID- 19542460
OWN - NLM
STAT- MEDLINE
DCOM- 20090820
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 183
IP  - 1
DP  - 2009 Jul 1
TI  - Downstream signals for MyD88-mediated phagocytosis of Borrelia burgdorferi can be 
      initiated by TRIF and are dependent on PI3K.
PG  - 491-8
LID - 10.4049/jimmunol.0900724 [doi]
AB  - We previously have shown that MyD88 is important for uptake of Borrelia 
      burgdorferi by bone marrow derived macrophages (BMDMs). The mechanism by which 
      MyD88 is involved in uptake of B. burgdorferi is currently is not well 
      characterized. Here, we report that MyD88-mediated defect in the phagocytosis of 
      B. burgdorferi can be complemented by TLR3/Toll/IL-1R domain-containing 
      adaptor-inducing IFN-beta (TRIF) activation in BMDMs from MyD88(-/-) mice. This 
      effect of TLR3/TRIF activation was not due to its induction of type I IFNs, 
      suggesting instead a convergence of signaling pathways downstream of MyD88 and 
      TRIF. To characterize signaling pathways involved in MyD88-mediated phagocytosis 
      of B. burgdorferi, BMDMs were treated with specific inhibitors of MAPK, protein 
      kinase C, JAK/STAT, or PI3K. Only inhibition of PI3K resulted in a significant 
      decrease of B. burgdorferi uptake. Consistent with this, B. burgdorferi 
      activation of MyD88 or TLR3/TRIF signaling resulted in increased activity of 
      PI3K. Additionally, association of B. burgdorferi with actin-related protein 
      (Arp2/3) complexes, which facilitate actin rearrangements during phagocytosis, 
      was similarly reduced in MyD88(-/-) BMDMs and in BMDMs treated with a PI3K 
      inhibitor. Taken together, these findings define an essential pathway whereby 
      downstream signals from MyD88 or TRIF converge on PI3K, which triggers actin 
      polymerization to initiate the phagocytosis of B. burgdorferi.
FAU - Shin, Ok S
AU  - Shin OS
AD  - Department of Pathology/Immunology, Tufts University, Boston, MA 02111, USA.
FAU - Miller, Lloyd S
AU  - Miller LS
FAU - Modlin, Robert L
AU  - Modlin RL
FAU - Akira, Shizuo
AU  - Akira S
FAU - Uematsu, Satoshi
AU  - Uematsu S
FAU - Hu, Linden T
AU  - Hu LT
LA  - eng
GR  - R01 AI050043-02/AI/NIAID NIH HHS/United States
GR  - R01 AI050043/AI/NIAID NIH HHS/United States
GR  - R01 AI050043-04/AI/NIAID NIH HHS/United States
GR  - R01 AI050043-01A1/AI/NIAID NIH HHS/United States
GR  - R01 AI050043-05/AI/NIAID NIH HHS/United States
GR  - R01AI050043/AI/NIAID NIH HHS/United States
GR  - R01 AI050043-03/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (TICAM-1 protein, mouse)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/*physiology
MH  - Animals
MH  - Bone Marrow Cells/enzymology/immunology/microbiology
MH  - Borrelia burgdorferi/*immunology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Enzyme Activation/immunology
MH  - Macrophages/enzymology/immunology/microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/deficiency/genetics/*physiology
MH  - Phagocytosis/genetics/*immunology
MH  - Phosphatidylinositol 3-Kinases/*metabolism/physiology
MH  - Poly I-C/pharmacology
MH  - Signal Transduction/genetics/*immunology
PMC - PMC2772066
MID - NIHMS152908
EDAT- 2009/06/23 09:00
MHDA- 2009/08/21 09:00
PMCR- 2010/07/01
CRDT- 2009/06/23 09:00
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2009/08/21 09:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - 183/1/491 [pii]
AID - 10.4049/jimmunol.0900724 [doi]
PST - ppublish
SO  - J Immunol. 2009 Jul 1;183(1):491-8. doi: 10.4049/jimmunol.0900724.