Expression profiling of host pathogen interactions: how Mycobacterium tuberculosis and the macrophage adapt to one another.
It has recently become feasible to quantify all mRNAs encoded by the genomes of bacterial pathogens and their eukaryotic host cells and to apply this approach to study the interaction of Mycobacterium tuberculosis with its primary host cell, the macrophage. These studies helped to identify regulatory circuits which mediate adaptation of the M. tuberculosis transcriptome to intraphagosomal environments and stimulated hypotheses for the function of these circuits in human tuberculosis. The macrophage transcriptome reacts to infections with the induction of a pathogen-unspecific expression program as well as the induction of pathogen-specific expression signatures, both of which contribute to the immunologic activation of the infected cell. M. tuberculosis induced changes in the macrophage transcriptome are mediated by Toll-like receptor dependent and Toll-like receptor independent signal transduction pathways. This response is shaped by macrophage produced reactive nitrogen and oxygen molecules and affected by viability and virulence of the pathogen.
Schnappinger
Dirk
D
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA. dis2003@med.cornell.edu
Schoolnik
Gary K
GK
Ehrt
Sabine
S
D000818:Animals; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D009569:Nitric Oxide / Q000378:metabolism; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology*; D014774:Virulence
D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D009569:Nitric Oxide