| First Author | Pai RK | Year | 2004 |
| Journal | Infect Immun | Volume | 72 |
| Issue | 11 | Pages | 6603-14 |
| PubMed ID | 15501793 | Mgi Jnum | J:93283 |
| Mgi Id | MGI:3056722 | Doi | 10.1128/IAI.72.11.6603-6614.2004 |
| Citation | Pai RK, et al. (2004) Prolonged toll-like receptor signaling by Mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Infect Immun 72(11):6603-14 |
| abstractText | Infection of macrophages with Mycobacterium tuberculosis or exposure to M. tuberculosis 19-kDa lipoprotein for >16 h inhibits gamma interferon (IFN-gamma)-induced major histocompatibility complex class II (MHC-II) expression by a mechanism involving Toll-like receptors (TLRs). M. tuberculosis was found to inhibit murine macrophage MHC-II antigen (Ag) processing activity induced by IFN-gamma but not by interleukin-4 (IL-4), suggesting inhibition of IFN-gamma-induced gene regulation. We designed an approach to test the ability of M. tuberculosis-infected cells to respond to IFN-gamma. To model chronic infection with M. tuberculosis with accompanying prolonged TLR signaling, macrophages were infected with M. tuberculosis or incubated with M. tuberculosis 19-kDa lipoprotein for 24 h prior to the addition of IFN-gamma. Microarray gene expression studies were then used to determine whether prolonged TLR signaling by M. tuberculosis broadly inhibits IFN-gamma regulation of macrophage gene expression. Of 347 IFN-gamma-induced genes, M. tuberculosis and 19-kDa lipoprotein inhibited induction of 42 and 36%, respectively. Key genes or gene products were also examined by quantitative reverse transcription-PCR and flow cytometry, confirming and extending the results obtained by microarray studies. M. tuberculosis inhibited IFN-gamma induction of genes involved in MHC-II Ag processing, Ag presentation, and recruitment of T cells. These effects were largely dependent on myeloid differentiation factor 88, implying a role for TLRs. Thus, prolonged TLR signaling by M. tuberculosis inhibits certain macrophage responses to IFN-gamma, particularly those related to MHC-II Ag presentation. This inhibition may promote M. tuberculosis evasion of T-cell responses and persistence of infection in tuberculosis. |
