Toll-Like Receptor 2 Is Required for Innate, But Not Acquired, Host Defense to Borrelia burgdorferi
| Autor: | James F. Zachary, Janis J. Weis, Alyson Yoder, R. Mark Wooten, Ying Ma, Carsten J. Kirschning, John H. Weis, Jeanette P. Brown |
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| Rok vydání: | 2002 |
| Předmět: |
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Bacterial Lipoproteins Immunology Receptors Cell Surface Mice Animals Drosophila Proteins Immunology and Allergy Borrelia burgdorferi Receptor Cells Cultured Mice Knockout Antigens Bacterial Mice Inbred C3H Toll-like receptor Membrane Glycoproteins biology Macrophages Toll-Like Receptors Lyme Disease Vaccines biology.organism_classification Antibodies Bacterial Toll-Like Receptor 2 Mice Inbred C57BL Bacterial vaccine Kinetics TLR2 Membrane glycoproteins Immunoglobulin class switching Antigens Surface Bacterial Vaccines biology.protein Cytokines Signal transduction Borrelia Infections Ankle Joint Bacterial Outer Membrane Proteins |
| Zdroj: | The Journal of Immunology. 168:348-355 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.168.1.348 |
| Popis: | Borrelia burgdorferi lipoproteins activate inflammatory cells through Toll-like receptor 2 (TLR2), suggesting that TLR2 could play a pivotal role in the host response to B. burgdorferi. TLR2 does play a critical role in host defense, as infected TLR2−/− mice harbored up to 100-fold more spirochetes in tissues than did TLR2+/+ littermates. Spirochetes persisted at extremely elevated levels in TLR2-deficient mice for at least 8 wk following infection. Infected TLR2−/− mice developed normal Borrelia-specific Ab responses, as measured by quantity of Borrelia-specific Ig isotypes, the kinetics of class switching to IgG, and the complexity of the Ags recognized. These findings indicate that the failure to control spirochete levels in tissues is not due to an impaired acquired immune response. While macrophages from TLR2−/− mice were not responsive to lipoproteins, they did respond to nonlipoprotein components of sonicated spirochetes. These TLR2-independent responses could play a role during the inflammatory response to B. burgdorferi, as infected TLR2−/− mice developed greater ankle swelling than wild-type littermates. Thus, while TLR2-dependent signaling pathways play a major role in the innate host defense to B. burgdorferi, both inflammatory responses and the development of the acquired humoral response can occur in the absence of TLR2. |
| Databáze: | OpenAIRE |
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