Laurel Lenz

Associate Professor Ph.D., University of Washington

Current Research

Our lab uses interdisciplinary approaches to study the interactions between intracellular bacterial pathogens and the host immune system. We manipulate both the pathogen and the host in order to define how specific microbial factors promote disease and influence immune responses. We primarily use as a model pathogen the Gram-positive bacterium, Listeria monocytogenes.

L. monocytogenes is an intracellular pathogen that infects and replicates within the cytosol of practically any animal cell. The bacterium secretes at least three virulence proteins that participate in disruption of phagosomes to allow the bacterial access to the host cell cytosol. Additional secreted and surface proteins of the bacterium promote bacterial nutrient acquisition, growth in the host cell cytosol, and use of the host cell’s actin cytoskeleton for bacterial cell-cell spread. L. monocytogenes shares genetic and physiological similarities with other deadly Gram-positive bacterial pathogens like Bacillus anthracis, Streptococci, Staphylococci, and Mycobacteria. The pathogenic strategies L. monocytogenes uses to infect the host cell cytosol are also similarity to those of pathogenic Francisella, Burkholderia, Rickettsia, and Shigella. Thus, studies using the L. monocytogenes model may contribute to our understanding of common features in these and other infectious and inflammatory diseases.

One focus of our current research is an investigation of how secreted bacterial proteins contribute to bacterial virulence and immune subversion. We recently showed that a secretion system called SecA2 contributes to secretion of at least nineteen L. monocytogenes proteins and is essential for L. monocytogenes virulence. SecA2-like proteins are also implicated in protein secretion and virulence in other important Gram-positive bacterial pathogens, such as M. tuberculosis. Our findings suggest that at least some SecA2-dependent proteins act to interfere with the host’s innate immune system, and we are actively investigating the basis for their effects on the host. We are also investigating other aspects of immune-modulation by pathogenic bacteria.

Recent Publications

Click Here For An Updated List Of Dr. Lentz's Publications

Muraille, E., Narni-Mancinelli, E., Gounon, P., Bassand, D., Glaichenhaus, N., Lenz, L.L., and Lauvau, G. (2007) “Cytosolic expression of SecA2 is a prerequisite for long-term protective immunity. ” Cell. Microbiol. 9:1445-54

Humann, J.L., Bjordahl, R., Andreasen, K., and Lenz, L.L. (2007) “Expression of the p60 autolysin enhances NK cell activation and is required for Listeria monocytogenes expansion in IFN-responsive mice.” J. Immunol. 178:2407-14.

Diehl, G.E., Yue, H.H., Hsieh, K., Ho, M., Kuang, A.A., Morici, L.A., Lenz, L.L., Cado, D., Riley, L.W., Winoto, A. (2004) “TRAIL-R as a negative regulator of innate immune responses.” Immunity. 21:1-20.

Lenz, L.L., Mohammadi, S., Geissler, A., and Portnoy, D.A. (2003) “SecA2-dependent secretion of autolytic enzymes promotes Listeria monocytogenes pathogenesis.” Proc. Nat. Acad. Sci. 100:12432-12437.

Lenz, L.L., and Portnoy, D.A. (2002) “Identification of a second L. monocytogenes secA gene that contributes to secretion and is associated with the rough phenotype.” Molec. Microbiol. 45:1043-1056.

Lenz, L.L., Butz, E., A, and Bevan, M.J. (2000) “Requirements for bone marrow-derived antigen-presenting cells in priming cytotoxic T cell responses to intracellular pathogens. J. Exp. Med. 192:1135-1142.