Logo for University of Iowa Health Care This logo represents the University of Iowa Health Care

Lee-Ann Allen, PhD

Internal Medicine and Microbiology and Immunology

Office: 505 EMRB
Office Phone: 319-335-4258

Lab: 500J EMRB

Lab Website: http://www.healthcare.uiowa.edu/programs/inflammation/

Pathogenesis of Helicobacter pylori and Francisella tularensis including manipulation of phagocyte function and immune dysregulation

Helicobacter pylori colonizes the gastric mucosa of 50% of all humans and elicits a chronic neutrophil-dominant inflammatory response that can progress to peptic ulceration or gastric cancer. H. pylori thrives in a neutrophil-rich environment, but how this is achieved is poorly defined. We recently discovered the capacity of H. pylori to induce subtype differentiation of human neutrophils, eliciting an N1-like phenotype that is defined by profound nuclear hypersegmentation, changes in surface markers and a cytotoxic and proinflammatory phenotype. Current projects focus on identification of the underlying mechanisms, including the identification of relevant virulence factors, and the functional consequences with respect to neutrophil manipulation of NK cell, T-cell, and epithelial cell function. Experimental approaches include studies of signaling, cytokine production, cell viability, and global transcriptional profiling via dual RNA-Seq.

Francisella tularensis is a facultative intracellular pathogen and the causative agent of the zoonotic disease tularemia. This bacterium infects several cell types including macrophages and neutrophils, and escapes the phagosome to replicate in the cytosol. In prior studies we identified receptors used by this organism to infect host cells, discovered multiple mechanisms used to disrupt neutrophil defense mechanisms, and characterized novel phenotypes of mutants with defects in capsule and LPS O-antigen production. We are now beginning new studies based on our discovery that F. tularensis elicits metabolic reprogramming of infected phagocytes, with a focus on studies of the relevant pathways and virulence factors, and elucidation of the functional consequences with respect to host cell survival and manipulation of the inflammatory response.

PubMed link

Department/Program Affiliations:
Internal Medicine
Microbiology and Immunology
Molecular Medicine