Effect of phthiocerol dimycocerosate deficiency on the transcriptional response of human macrophages to Mycobacterium tuberculosis.
The control of mycobacterial infections is dependent on the finely tuned synergism between the innate and adaptive immune responses. The macrophage is the major host cell for Mycobacterium tuberculosis and the degree of virulence of mycobacteria may influence the initial macrophage response to infection. The cell wall molecule, phthiocerol dimycocerosate (DIM), is an important virulence factor that influences the early growth of M. tuberculosis in the lungs. To explore the basis for this effect we have compared the early gene response of human THP-1 macrophages to infection with virulent M. tuberculosis and the DIM-deficient DeltafadD26 M. tuberculosis strain using microarrays. Detailed analysis revealed a common core of macrophage genes, which were rapidly induced following infection with both strains, and deficiency of DIM had no significant effect on this initial macrophage transcriptional responses. In addition to chemokines and pro-inflammatory cytokines, the early response genes included components of the Toll-like receptor signalling, antigen presentation and apoptotic pathways, interferon response genes, cell surface receptors and their ligands, including TNF-related apoptosis inducing ligand (TRAIL) and CD40, and other novel genes. Therefore, although fadD26 deficiency is responsible for the early attenuation of the growth of M. tuberculosis in vivo, this effect is not associated with differences in the initial macrophage transcriptional response.
Scandurra
G M
GM
Mycobacterial Research Group, Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag No. 6, Newtown, NSW 2042, Australia.
Williams
R B H
RB
Triccas
J A
JA
Pinto
R
R
Gicquel
B
B
Slobedman
B
B
Cunningham
A
A
Britton
W J
WJ
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000172:deficiency*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015533:Transcriptional Activation; D037521:Virulence Factors / Q000276:immunology
D000942:Antigens, Bacterial; D008055:Lipids; D037521:Virulence Factors; C008901:phthiocerol dimycocerosate