The Journal of Immunology · 2000 · 1K citations · 21 references
Life SciencesImmunologyMicrobiologyHost-pathogen InteractionsInnate ImmunityMicrobial PathogenesisBacterial InfectionsBacterial PathogenesisInnate Immune ReceptorsInnate Immune ResponseSusceptibility To InfectionToll-like ReceptorsGram-positive Bacterial InfectionsImmune Response To Bacterial InfectionMacrophage Toll-like Receptor SignalingMyd88-dependent SignalingPathogen-associated Molecular PatternsPeritoneal MacrophagesToll-like Receptor SignalingToll-like Receptor-mediated Innate Immune Response
Toll-like receptor (TLR) family acts as pattern recognition receptors for pathogen-specific molecular patterns. We previously showed that TLR2 recognizes Gram-positive bacterial components whereas TLR4 recognizes LPS, a component of Gram-negative bacteria. MyD88 is shown to be an adaptor molecule essential for TLR family signaling. To investigate the role of TLR family in host defense against Gram-positive bacteria, we infected TLR2- and MyD88-deficient mice with Staphylococcus aureus. Both TLR2- and MyD88-deficient mice were highly susceptible to S. aureus infection, with more enhanced susceptibility in MyD88-deficient mice. Peritoneal macrophages from MyD88-deficient mice did not produce any detectable levels of cytokines in response to S. aureus. In contrast, TLR2-deficient macrophages produced reduced, but significant, levels of the cytokines, and TLR4-deficient macrophages produced the same amounts as wild-type cells, indicating that S. aureus is recognized not only by TLR2, but also by other TLR family members except for TLR4.
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Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in <i>Tlr4</i> Gene
Alexander Poltorak, Xiaolong He, Irina Smirnova et al. · Science · 1998 · 7.6K citations
Katsuaki Hoshino, Osamu Takeuchi, Taro Kawai et al. · The Journal of Immunology · 1999 · 3.4K citations · Full text
Life Sciences, Genetics, Immunology +15
Unresponsiveness of MyD88-Deficient Mice to Endotoxin
Taro Kawai, Osamu Adachi, Tomohiko Ogawa et al. · Immunity · 1999 · 2.1K citations · Full text