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Schlesinger, Larry
M. tuberculosis and non-tuberculous mycobacteria are highly prevalent human pathogens worldwide which cause significant morbidity and mortality, particularly in AIDS patients. They are intracellular pathogens of mononuclear phagocytes. Dr. Schlesinger’s research focuses on innate immunity in mycobacterial infections by studying human mononuclear phagocyte interactions with pathogenic mycobacteria, particularly M. tuberculosis. The laboratory uses a variety of approaches (cell biology, immunology, molecular biology and biochemistry) to study the role of mycobacterial surface glycoconjugates in complement activation and in binding to phagocyte receptors. It also focuses on the mechanism of phagocytosis of mycobacteria by macrophages, the intracellular trafficking pathway of mycobacterial products and the ability of intracellular mycobacteria to regulate the biosynthesis and expression of macrophage class II molecules, accessory molecules for antigen presentation and molecules involved in cellular adhesion. The laboratory utilizes novel in-vitro models that include surfactant components to study innate immune responses to these pathogens in the air spaces of the lung. Finally, the lab studies the iron-dependent metabolic pathways in mycobacteria by using trivalent metals to inhibit these pathways. Newly characterized clinical isolates of M. tuberculosis and mutant strains of bacteria are utilized for these studies. Selected Publications Torrelles JB, Azad AK, Schlesinger LS. Fine discrimination in the recognition of individual species of phosphatidyl-myo-inositol mannosides from Mycobacterium tuberculosis by C-type lectin pattern recognition receptors. J. Immunol. 177:1805-1816, 2006. Parsa KVL, Ganesan LP, Rajaram MVS, Gavrilin MA, Wewers MD, Schlesinger LS, Gunn JS, Tridandapani S. Macrophage pro-inflammatory response to Francisella novicida infection is regulated by the SH2 domain-containing inositol 5’ phosphatase SHIP. PLOS Pathogens 2:0681-0690, 2006. Balagopal A, MacFarlane AS, Mohapatra N, Soni S, Gunn JS, Schlesinger LS. Characterization of the receptor-ligand pathways important for entry and survival of Francisella tularensis in human macrophages. Infect. Immun. 74: 5114-5125, 2006. Olakanmi O, Schlesinger LS, and Britigan BE. Hereditary hemochromatosis results in decreased iron acquisition and growth by Mycobacterium tuberculosis within human macrophages. J Leuko Bio 81:195-204, 2007. Mohaptra NP, Balagopal A, Soni S, Schlesinger LS, Gunn JS. AcpA is a Francisella Acid Phosphatase that affects Intramacrophage Survival and Virulence. Infect. Immun. 75: 390-396, 2007. Young JD, Balagopal A, Reddy NS, Schlesinger LS. Pulmonary infections caused by non-tuberculous mycobacteria: An update on epidemiology, diagnosis, and treatment. J. Resp. Dis 28: 7-18, 2007. Butchar JP, Rajaram MVS, Ganesan LP, Parsa KVL, Clay CD, Schlesinger LS, Tridandapani S. Francisella tularensis induces Interleukin-23 production in human monocytes. J. Immunol. 178:4445-4454, 2007. Schlesinger Laboratory Personnel
Contact 1004 BRT Links Divison of Infectious Diseases
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Larry S. Schlesinger, MD, is Director of the CMIB and the Division of Infectious Diseases. Dr. Schlesinger is Professor of Internal Medicine and Molecular Virology, Immunology, and Medical Genetics. He joined the faculty in 2002. He is a member of the Integrated Biomedical Science Graduate Program. He is recipient of awards from the American Lung Association, Department of Veterans Affairs, and NIH for work with M. tuberculosis. He is recipient of a 1993 ICAAC Young Investigator Award and has served as Chair of the Tuberculosis section for the American Society for Microbiology and the Infectious Diseases Society of America.