Containment of aerogenicMycobacterium tuberculosis infection in mice does not require MyD88 adaptor function for TLR2, -4 and -9
| Autor: | Clara Bathmann, Norbert Reiling, Stefan Ehlers, Tanja Sonntag, Alexandra Hölscher, Marina A. Freudenberg, Daniel S. Korbel, Shizuo Akira, Christoph Hölscher, Ulrich E. Schaible, Horst Mossmann, Hermann Wagner, Carsten J. Kirschning, Insa Lenz, Svenja Kröger |
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| Rok vydání: | 2008 |
| Předmět: |
Lipopolysaccharides
T-Lymphocytes T cell Immunology Gene Expression Nitric Oxide Synthase Type II Biology Microbiology Mycobacterium tuberculosis Interferon-gamma Mice Immune system GTP-Binding Proteins Immunity medicine Animals Tuberculosis Immunology and Allergy Macrophage Lung Mice Knockout Immunity Cellular Tumor Necrosis Factor-alpha Macrophages Animal Structures TLR9 biology.organism_classification Immunity Innate Toll-Like Receptor 2 Mice Inbred C57BL Toll-Like Receptor 4 TLR2 medicine.anatomical_structure Oligodeoxyribonucleotides Toll-Like Receptor 9 Myeloid Differentiation Factor 88 TLR4 Cytokines |
| Zdroj: | European Journal of Immunology. 38:680-694 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.200736458 |
| Popis: | The role of Toll-like receptors (TLR) and MyD88 for immune responses to Mycobacterium tuberculosis (Mtb) infection remains controversial. To address the impact of TLR-mediated pathogen recognition and MyD88-dependent signaling events on anti-mycobacterial host responses, we analyzed the outcome of Mtb infection in TLR2/4/9 triple- and MyD88-deficient mice. After aerosol infection, both TLR2/4/9-deficient and wild-type mice expressed pro-inflammatory cytokines promoting antigen-specific T cells and the production of IFN-gamma to similar extents. Moreover, TLR2/4/9-deficient mice expressed IFN-gamma-dependent inducible nitric oxide synthase and LRG-47 in infected lungs. MyD88-deficient mice expressed pro-inflammatory cytokines and were shown to expand IFN-gamma-producing antigen-specific T cells, albeit in a delayed fashion. Only mice that were deficient for MyD88 rapidly succumbed to unrestrained mycobacterial growth, whereas TLR2/4/9-deficient mice controlled Mtb replication. IFN-gamma-dependent restriction of mycobacterial growth was severely impaired only in Mtb-infected MyD88, but not in TLR2/4/9-deficient bone marrow-derived macrophages. Our results demonstrate that after Mtb infection neither TLR2, -4, and -9, nor MyD88 are required for the induction of adaptive T cell responses. Rather, MyD88, but not TLR2, TLR4 and TLR9, is critical for triggering macrophage effector mechanisms central to anti-mycobacterial defense. |
| Databáze: | OpenAIRE |
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