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Department of Immunology
Lynn Hajjar obtained her DVM in 1988 from the University of Illinois. She then continued her graduate studies in the laboratory of Maxine Linial at the Fred Hutchinson Cancer Research Center in Seattle and obtained a PhD in 1995 from the University of Washington. She also completed a residency in Laboratory Animal Medicine in 1992 at the University of Washington. She had one year of postdoctoral training in the laboratory of Julie Overbaugh before joining Chris Wilson’s laboratory where she is currently a Research Associate Professor. Toll-like receptors are pattern-recognition receptors that recognize molecular patterns expressed by microbial organisms. This family of receptors mediates early innate responses. We are interested in understanding how specificity is achieved in this “non-antigen-specific” response. Toll-like receptor 4 (TLR4) and its coreceptor MD-2 recognize the lipid A component of lipopolysaccharide (LPS) which comprises the outer leaflet of the outer membrane of Gram negative bacteria. It is now clear that the structure of lipid A varies not only between bacterial genotypes but also within a species grown under different conditions. We and others have shown that mouse and human TLR4/MD-2 differentially recognize lipid A structures, with the human receptor being hyporesponsive to penta- and tetra-acylated lipid A. For example, Yersinia pestis produces a hexa-acylated structure at room temp (flea temperature) and switches to a tetra-acylated structure at 37°C (mammalian temperature). This tetra-acylated structure is an agonist to the mouse TLR4/MD-2 receptor but an antagonist to the human receptor. We hypothesize that this switching to a tetra-acylated LPS structure by Y. pestis at 37°C is an immune evasion strategy that makes humans more susceptible to infection than mice. We have generated mice that express the human receptors instead of the mouse receptors to determine the biological consequences of the difference in recognition of LPS structures in various models of infection and immunization. Representative publications: Hajjar AM*, Ernst RK*, Tsai JH, Wilson CB**, Miller SI**. Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nature Immunol 3:354-359, 2002. Ernst RK, Hajjar AM, Tsai JH, Moskowitz SM, Wilson CB, Miller SI. Pseudomonas aeruginosa lipid A diversity and its recognition by Toll-like receptor 4. J Endotoxin Res 9:395-400, 2003. Darveau RP, Pham TT, Lemley K, Reife RA, Bainbridge BW, Coats SR, Howald WN, Way SS, Hajjar AM. Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4. Infect Immun 72:5041–5051, 2004. Hajjar AM, Harowicz H, Liggitt HD, Fink PJ, Wilson CB, Skerrett SJ. An essential role for non-bone marrow-derived cells in control of Pseudomonas aeruginosa pneumonia. Am J Respir Cell Mol Biol 33:470-5, 2005. Krishnegowda G*, Hajjar AM* **, Zhu J, Douglass EJ, Uematsu S, Akira S, Woods AS, Gowda DC**. Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity. J Biol Chem 280:8606-16, 2005. Hajjar AM, Harvey MD, Shaffer SA, Goodlett DR, Sjostedt A, Edebro H, Forsman M, Bystrom M, Pelletier M, Wilson CB, Miller SI, Skerrett SJ, Ernst RK. Lack of in vitro and in vivo recognition of Francisella subspecies LPS by Toll-like receptors. Infect Immun 74:6730-8, 2006. Kanistanon D, Hajjar AM, Pelletier MR, Gallagher LA, Kalhorn T, Shaffer SA, Goodlett DR, Rohmer L, Brittnacher MJ, Skerrett SJ, Ernst RK. A Francisella mutant in Lipid A carbohydrate modification elicits protective immunity. PLoS Pathog 4:e24, 2008.
*contributed equally **share senior authorship Updated July 2008
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