title: MyDths and un-TOLLed truths: sensor, instructive and effector immunity to tuberculosis.
abstract: Controversy exists concerning the role of Toll-like receptors and MyD88 in immunity to tuberculosis (TB). This mini-review argues that (i) Toll-like receptors are not essential for an effective immune response against TB, (ii) MyD88 is essential, but not because it transduces signals from TLRs, (iii) adaptive immunity to TB is largely TLR/MyD88-independent. Some of the discrepancies may be resolved by cogent attribution of distinct immune functions to the individual components of the TLR/MyD88 system. In mice, TLRs and MyD88 are fully dispensable in sensing Mtb infection and instructing T cell-mediated adaptive immunity, and while TLRs are also redundant during macrophage effector immunity, MyD88 is essential for efficient killing of mycobacteria. This distinction should help to molecularly pinpoint the MyD88-dependent, yet TLR-independent critical mechanisms of macrophage activation involved in intracellular growth restriction of Mtb. Disrupted IL-1R and/or IFN-gamma signaling pathways likely play a much more prominent role in explaining the exquisite susceptibility of MyD88-deficient mice to TB than the function of MyD88 as a TLR adaptor.
authors.affiliation: Microbial Interface Biology, Research Center Borstel, D-23845 Borstel, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Reiling
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehlers
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
mesh_terms: D000818:Animals; D003713:Dendritic Cells; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000819:agonists / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D046709:Pattern Recognition, Physiological; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000172:deficiency / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D018836:Inflammation Mediators; D007375:Interleukin-1; D053594:Myeloid Differentiation Factor 88; D053573:Receptors, Interleukin-1 Type I; D051193:Toll-Like Receptors; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases