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The roles of MyD88, TLR2, TLR5, and TLR9 in phagocytosis and inflammatory signaling by Borrelia burgdorferi
Author(s) -
Shin Sarah Ok,
Behera Aruna,
Hu Linden
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.675.5
Subject(s) - tlr5 , borrelia burgdorferi , tlr2 , phagocytosis , tlr9 , tlr7 , cytochalasin d , microbiology and biotechnology , toll like receptor , tlr4 , chemistry , signal transduction , biology , immunology , receptor , innate immune system , cell , biochemistry , antibody , gene expression , cytoskeleton , gene , dna methylation
The role of TLR signaling in the phagocytosis of Borrelia burgdorferi is just beginning to be studied. Here, we show that bone marrow derived macrophages (BMDM) from MyD88 deficient mice were unable to efficiently internalize the B. burgdorferi. Transfection of a MyD88 dominant negative plasmid into Raw264.7 cells produced similar results on phagocytosis. Loss of TLR2, TLR5 and TLR9in BMDM produced no defects in phagocytosis of B. burgdorferi . Release of inflammatory cytokines was greatly diminished in MyD88 −/− BMDM cells in response to B. burgdorferi , but only partially affected in TLR2 −/− BMDM. Cytochalasin D inhibition of phagocytosis reduced inflammatory signaling significantly, but not to the level of the MyD88 −/− BMDM. Addition of cytochalasin D to TLR2 −/− BMDM inhibited inflammatory responses to B. burgdorferi to the level of MyD88 −/− BMDM consistent with contributions from both recognition of external products and lysosomal sampling by TLR2 to inflammatory signaling. TLR5 also contributes to inflammatory signaling in response to B. burgdorferi . Taken together, these results show that MyD88, but not TLR2, TLR5 and TLR9, is important for the uptake of B. burgdorferi and MyD88 affects inflammatory responses both through its effects on phagocytosis and its role in transducing signals from TLR2 and TLR5. (RO1 AI50043)