Lee-Ann H. Allen, Ph.D.
Ph.D., Biochemistry, University of Wisconsin-Madison, 1990 |
Associate Professor of Medicine and Microbiology Campus address: Inflammation Program D-154 MTF Mailing address: 2501 Crosspark Rd. D-154 MTF Coralville, IA 52241 Phone: 319-335-4258 Email: |
Perturbation of Phagocyte Function by Bacterial Pathogens
Research in my laboratory studies the pathogenesis of mechanisms of pathogenesis of two Gram-negative bacteria - Helicobacter pylori and Franicsella tularensis.
Helicobacter pylori colonizes the gastric epithelium of up to half the world’s population and plays a causative role in the development of peptic ulcers and gastric cancer. One hallmark of H. pylori is its persistence. H. pylori infection causes a massive influx of neutrophils (PMNs) and mononuclear cells into the gastric mucosa, chronic gastritis and damage to host tissue, but the immune response does not resolve the infection and the reasons for this host-defense defect are unclear. Our long-term goal is to determine at the molecular level how H. pylori avoids being killed by the host innate immune system with a particular focus on bacteria-phagocyte interactions. At the present time our research on this topic can be divided into three main areas. 1) Molecular characterization of the H. pylori phagosome. 2) Identification of H. pylori virulence genes important for bacterial survival inside phagocytes. 3) Characterization of the mechanism(s) by which H. pylori activates neutrophils and disrupts granule targeting.
Francisella tularensis is a facultative intracellular pathogen and the causative agent of tularemia. Interest in this organism has increased recently because of its potential use as a bioweapon. It has long been known that Francisella replicates inside macrophages, and recent data indicate that, several hours after uptake, bacteria escape the phagosome and replicate in the macrophage cytosol. We have identified two receptors that mediate entry of this organism into human macrophages and are beginning to define the composition of the compartment from which it escapes. In addition, we are also studying the fate of Francisella in other cell types, particularly neutrophils. In the last year we have shown that Francisella evades elimination by human neutrophils and our data suggest a model in which early inhibition of the respiratory burst allows Francisella to escape the neutrophil phagosome and persist in the nutrient rich cytosol. Dissecting how Francisella inhibits neutrophil (and macrophage) function are areas of active investigation in my laboratory.
Inflammation Program
Recent publications
Allen, L.-A.H. 2007. Immunofluorescence and confocal microscopy of neutrophils. Methods Mol Biol (in press).
Allen, L.-A.H. 2007. Phagocytosis and persistence of Helicobacter pylori. Cell Microbiol (in press).
Nakano, Y., B. Banfi, A.J. Jesiatis, M.C. Dinauer, L.-A.H. Allen, and W.M. Nauseef. 2007. Critical roles for p22phox in the structural maturation and subcellular targeting of Nox3. Biochem J (in press).
Schulert, G.S., and L.-A.H. Allen. 2006. Differential infection of mononuclear phagocytes by Francisella tularensis: role of the macrophage mannose receptor. J Leukoc Biol 80:563-5771.
McCaffrey, R.L., and L.-A.H. Allen. 2006. Pivotal Advance: Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape. J Leukoc Biol 80:1224-1230.