Induction of macrophage-derived SLPI by Mycobacterium tuberculosis depends on TLR2 but not MyD88.

TitleInduction of macrophage-derived SLPI by Mycobacterium tuberculosis depends on TLR2 but not MyD88.
Publication TypeJournal Article
Year of Publication2005
AuthorsDing A, Yu H, Yang J, Shi S, Ehrt S
Date Published2005 Nov
KeywordsAdaptor Proteins, Signal Transducing, Animals, Antigens, Bacterial, Antigens, Differentiation, Blotting, Northern, Interferon-gamma, Lung, Macrophages, Peritoneal, Mice, Mice, Inbred C57BL, Mycobacterium tuberculosis, Myeloid Differentiation Factor 88, Proteinase Inhibitory Proteins, Secretory, Proteins, Receptors, Immunologic, Reverse Transcriptase Polymerase Chain Reaction, Secretory Leukocyte Peptidase Inhibitor, Signal Transduction, Toll-Like Receptor 2, Toll-Like Receptor 4, Tuberculosis, Pulmonary, Tumor Necrosis Factor-alpha

Macrophages respond to Mycobacterium tuberculosis by regulating expression of gene products that initiate a host innate response to this micro-organism. In this study, we report that exposure of murine peritoneal macrophages to heat-killed Mycobacterium tuberculosis (HK-Mtb) led to an increase in secretory leucocyte protease inhibitor (SLPI) gene expression and protein secretion in a time- and dose-dependent manner. HK-Mtb-induced SLPI mRNA expression was sensitive neither to a protein synthesis inhibitor, cycloheximide, nor to an actin polymerization blocker, cytochalasin D. Treatment of macrophages with interferon (IFN)-gamma inhibited HK-Mtb-induced SLPI expression. RAW264.7 cells stably expressing SLPI produced a reduced level of tumour necrosis factor (TNF) in response to HK-Mtb as compared with mock transfectants. Aerosol infection of mice with live M. tuberculosis resulted in an induction of SLPI gene expression in infected lungs. Macrophages from Toll-like receptor 4 (TLR4)-/- or MyD88-/- mice responded to M. tuberculosis similarly to wild-type macrophages by exhibiting increased SLPI expression. In contrast, macrophages from TLR2-/- mice were incapable of inducing SLPI in response to M. tuberculosis. This induction signifies the presence of a TLR2-dependent but MyD88-independent M. tuberculosis signalling pathway, suggesting involvement of adaptor protein(s) other than MyD88 in M. tuberculosis-mediated induction of SLPI.

Alternate JournalImmunology
PubMed ID16236128
PubMed Central IDPMC1802419
Grant ListGM61710 / GM / NIGMS NIH HHS / United States
R01 AI030165 / AI / NIAID NIH HHS / United States
R01 GM061710 / GM / NIGMS NIH HHS / United States
R01 HL068525 / HL / NHLBI NIH HHS / United States
AI30165 / AI / NIAID NIH HHS / United States

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