Distinct Roles for MyD88 and Toll-Like Receptors 2, 5, and 9 in Phagocytosis ofBorrelia burgdorferiand Cytokine Induction
Inflammation
Mice, Knockout
0301 basic medicine
0303 health sciences
Lipoproteins
Macrophages
p38 Mitogen-Activated Protein Kinases
Toll-Like Receptor 2
Cell Line
Mice
Toll-Like Receptor 5
03 medical and health sciences
Bacterial Proteins
Gene Expression Regulation
Phagocytosis
Borrelia burgdorferi
Toll-Like Receptor 9
Myeloid Differentiation Factor 88
Animals
Cytokines
RNA Interference
RNA, Small Interfering
Signal Transduction
DOI:
10.1128/iai.01600-07
Publication Date:
2008-04-01T00:45:18Z
AUTHORS (6)
ABSTRACT
ABSTRACTThe contribution of Toll-like receptors (TLRs) to phagocytosis ofBorrelia burgdorferihas 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. burgdorferito 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. burgdorferiand that MyD88 affects inflammatory responses through both its effects on phagocytosis and its role in transducing signals from TLR2 and TLR5.
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