The Ernst lab works on several aspects of the interaction of host and pathogen in tuberculosis and other infectious diseases. There are currently three major projects in the lab.

The first project focuses on the initial interactions of Mycobacterium tuberculosis with host cells invivo, and has identified distinct subsets of cells that are the direct targets of these bacteria in the lung and secondary lymphoid tissues. In addition, this project is working to identify the cells that initiate cellular immune responses to M. tuberculosis after aerosol infection, and to identify the cells that harbor intracellular bacteria during chronic infection. We hypothesize that these latter cells provide a sanctuary for the bacteria, where they are sequestered from recognition and elimination by cellular immune responses.

The second project concentrates on understanding the molecular mechanisms used by M. tuberculosis to avoid elimination by the immune response. Work on this project has revealed that M. tuberculosis makes macrophages resistant to activation by interferon gamma, and that it does so by inhibiting the signal transduction pathway initiated by interferon gamma to regulate specific genes. In addition, we have identified the components of M. tuberculosis that are responsible for initiating the inhibition of responses to interferon gamma, and we have determined that they act through pathways that overlap with those of the innate immune response. We hypothesize that mechanisms to overcome the inhibition of responses to interferon gamma will make the immune response to M. tuberculosis more effective, and may be essential for an improved vaccine against tuberculosis.

The third project studies expression of M. tuberculosis genes during distinct phases of infection in vivo. By using a combination of studies in model systems, and gene expression analysis by microarray and quantitative RT-PCR, we are developing evidence that M. tuberculosis induces expression of specific genes late in infection. We hypothesize that the products of these genes are not recognized by the immune system because the antigen-presenting cells that contain them are sequestered in granulomas, and that the products are involved in allowingM. tuberculosis to persist and progress, despite a cellular immune response to early antigens. The long range goals of this project are to identify potential novel drug targets, and to provide a foundation for design of an effective vaccine against tuberculosis.
A recent web presentation that gives additional information on research in the Ernst Laboratory is available at http://www.nyas.org/ebriefreps/splash.asp?intEbriefID=483.