Open AccessDistinct Roles for MyD88 and Toll-Like Receptors 2, 5, and 9 in Phagocytosis ofBorrelia burgdorferiand Cytokine Induction
Author(s) -
Ok Sarah Shin,
Ralph R. Isberg,
Shizuo Akira,
Satoshi Uematsu,
Aruna K. Behera,
Linden T. Hu
Publication year - 2008
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01600-07
Subject(s) - borrelia burgdorferi , biology , microbiology and biotechnology , phagocytosis , cytokine , receptor , toll , toll like receptor , virology , immunology , innate immune system , antibody , genetics
The contribution of Toll-like receptors (TLRs) to phagocytosis ofBorrelia burgdorferi has not been extensively studied. We show that bone marrow-derived macrophages (BMDM) from MyD88−/− mice or Raw cells transfected with a dominant-negative MyD88 were unable to efficiently internalizeB. burgdorferi. Knockouts of TLR2 and TLR9 or knockdown of TLR5 by small interfering RNA produced no defects in phagocytosis ofB. burgdorferi . Production of inflammatory cytokines was greatly diminished in MyD88−/− BMDM but only partially affected in TLR2−/− BMDM or knockdown of TLR5 and unaffected in TLR9−/− BMDM. Cytochalasin D reduced cytokine induction, but not to the level of the MyD88−/− BMDM. Addition of cytochalasin D to TLR2−/− BMDM inhibited inflammatory responses toB. burgdorferi to the level of MyD88−/− BMDM, consistent with a role for TLR2 in both recognition of extracellular products and lysosomal sampling by TLR2 after processing of the organism. Cytochalasin D had no impact on cytokine production in cells undergoing TLR5 knockdown. These results suggest that MyD88, but not TLR2, TLR5, and TLR9, is important for the uptake ofB. burgdorferi and that MyD88 affects inflammatory responses through both its effects on phagocytosis and its role in transducing signals from TLR2 and TLR5.