Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages.
BACKGROUND
Transcriptional profiling using microarrays provides a unique opportunity to decipher host pathogen cross-talk on the global level. Here, for the first time, we have been able to investigate gene expression changes in both Mycobacterium tuberculosis, a major human pathogen, and its human host cells, macrophages and dendritic cells.


RESULTS
In addition to common responses, we could identify eukaryotic and microbial transcriptional signatures that are specific to the cell type involved in the infection process. In particular M. tuberculosis shows a marked stress response when inside dendritic cells, which is in accordance with the low permissivity of these specialized phagocytes to the tubercle bacillus and to other pathogens. In contrast, the mycobacterial transcriptome inside macrophages reflects that of replicating bacteria. On the host cell side, differential responses to infection in macrophages and dendritic cells were identified in genes involved in oxidative stress, intracellular vesicle trafficking and phagosome acidification.


CONCLUSIONS
This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments.
Tailleux
Ludovic
L
Institut Pasteur, Unit of Mycobacterial Genetics, Paris, France.
Waddell
Simon J
SJ
Pelizzola
Mattia
M
Mortellaro
Alessandra
A
Withers
Michael
M
Tanne
Antoine
A
Castagnoli
Paola Ricciardi
PR
Gicquel
Brigitte
B
Stoker
Neil G
NG
Butcher
Philip D
PD
Foti
Maria
M
Neyrolles
Olivier
O
D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology*; D020869:Gene Expression Profiling; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D014158:Transcription, Genetic