TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis
By A. Báfica, C. Scanga, C. Feng, C. Leifer, A. Cheever, A. Sher. Journal of Experimental Medicine, 2005
665 citations recorded by the source corpus.
To investigate the role of Toll-like receptor (TLR)9 in the immune response to mycobacteria as well as its cooperation with TLR2, a receptor known to be triggered by several major mycobacterial ligands, we analyzed the resistance of TLR9−/− as well as TLR2/9 double knockout mice to aerosol infection with Mycobacterium tuberculosis. Infected TLR9−/− but not TLR2−/− mice displayed defective mycobacteria-induced interleukin (IL)-12p40 and interferon (IFN)-γ responses in vivo, but in common with TLR2−/− animals, the TLR9−/− mice exhibited only minor reductions in acute resistance to low dose pathogen challenge. When compared with either of the single TLR-deficient animals, TLR2/9−/− mice displayed markedly enhanced susceptibility to infection in association with combined defects in proinflammatory cytokine production in vitro, IFN-γ recall responses ex vivo, and altered pulmonary pathology. Cooperation between TLR9 and TLR2 was also evident at the level of the in vitro response to live M. tuberculosis, where dendritic cells and macrophages from TLR2/9−/− mice exhibited a greater defect in IL-12 response than the equivalent cell populations from single TLR9-deficient animals. These findings reveal a previously unappreciated role for TLR9 in the host response to M. tuberculosis and illustrate TLR collaboration in host resistance to a major human pathogen.
Subfields: Immunology, Infectious Diseases
View Paper: https://www.semanticscholar.org/paper/ae7b549301ca79dbc033e5485b12110e91b0f8d4
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Citations in the corpus
- The Role of TLR2 in Infection and Immunity (2012, background): “Murine phagocytes with impaired TLR2 function, either by using blocking antibodies or gene knockouts, when exposed to the above bacteria or their cell wall components have diminished or absent production of TNF-α or/and IL-6, as opposed to normal cells (Takeuchi et al., 1999, 2000; Torres et al., 20”
- Pyruvate Kinase M2 regulates Hif-1α activity and IL-1β induction, and is a critical determinant of the Warburg Effect in LPS-activated macrophages (2015, neutral): “As the main causative agent of tuberculosis, Mtb signals mainly through TLR 2, 6 and 9 (Bafica et al., 2005; Means et al., 1999).”
- Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses (2009, background): “Increasing evidence suggests that TLR9 activation by unmethylated CpG DNA derived from bacterial genomes also plays an important role during infection with gram-negative bacteria, frequently in cooperation with other PRRs (26, 262).”