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Induction of macrophage‐derived SLPI by Mycobacterium tuberculosis depends on TLR2 but not MyD88
Author(s) -
Ding Aihao,
Yu Hongwei,
Yang Jingxuan,
Shi Shuangping,
Ehrt Sabine
Publication year - 2005
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02238.x
Subject(s) - slpi , tlr2 , biology , mycobacterium tuberculosis , microbiology and biotechnology , cycloheximide , tlr4 , immunology , tuberculosis , inflammation , protein biosynthesis , medicine , pathology
Summary 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)‐γ 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.