Downstream signals for MyD88-mediated phagocytosis of Borrelia burgdorferi can be initiated by TRIF and are dependent on PI3K

Ok Shin, Lloyd S. Miller, Robert L. Modlin, Shizuo Akira, Satoshi Uematsu, Linden T. Hu

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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-β (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.

Original languageEnglish
Pages (from-to)491-498
Number of pages8
JournalJournal of Immunology
Volume183
Issue number1
DOIs
Publication statusPublished - 2009 Jul 1
Externally publishedYes

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Borrelia burgdorferi
Phosphatidylinositol 3-Kinases
Phagocytosis
Macrophages
Actin-Related Protein 3
Actins
Actin-Related Protein 2-3 Complex
Mitogen-Activated Protein Kinase Kinases
Polymerization
Protein Kinase C

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Downstream signals for MyD88-mediated phagocytosis of Borrelia burgdorferi can be initiated by TRIF and are dependent on PI3K. / Shin, Ok; Miller, Lloyd S.; Modlin, Robert L.; Akira, Shizuo; Uematsu, Satoshi; Hu, Linden T.

In: Journal of Immunology, Vol. 183, No. 1, 01.07.2009, p. 491-498.

Research output: Contribution to journalArticle

Shin, Ok ; Miller, Lloyd S. ; Modlin, Robert L. ; Akira, Shizuo ; Uematsu, Satoshi ; Hu, Linden T. / Downstream signals for MyD88-mediated phagocytosis of Borrelia burgdorferi can be initiated by TRIF and are dependent on PI3K. In: Journal of Immunology. 2009 ; Vol. 183, No. 1. pp. 491-498.
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