Schlesinger, Larry S.

Larry S. Schlesinger, M.D.

Professor and Division Director
Department of Internal Medicine, Division of Infectious Diseases

Joint Appointment
Department of Molecular Virology, Immunology and Medical Genetics

For More Information:
See Dr. Schlesinger's webpage

Contact
e-mail: schlesinger-2@medctr.osu.edu
phone: 614-293-8636
http://cmib.osu.edu
216 Tzagournis Medical Research Facility
420 W. 12 Ave.
Columbus OH  43210

Larry S. Schlesinger, MD, is Director of the CMIB and the Division of Infectious Diseases.  Larry 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 and the Department of Veterinary Biosciences. 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.

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.  The lab also 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. Finally, the lab is interested in pathogenesis of the category A biodefense agent, Francisella tularensis.  This work involves examining receptor-mediated interactions between the bacteria and human macrophages.

DesJardin LE, Kaufman TM, Potts B, Kutzbach B, Yi H, Schlesinger LS.  M. tuberculosis-infected human macrophages exhibit enhanced cellular adhesion with increased expression of LFA-1 and ICAM-1 and reduced expression and/or function of complement receptors, FcgRII and the mannose receptor Microbiology 148:3161-3171, 2002.

Ferguson JS, Weis JJ, Martin JL, Schlesinger LS. Complement protein C3 binding to Mycobacterium tuberculosis is initiated by the classical pathway in human bronchoalveolar lavage fluid. Infect. Immun. 72:2564-2573, 2004.

Crowther JE, Kutala, VK, Kuppusamy, P, Ferguson, JS, Beharka, AA, Zweier, JL, McCormack, FX, Schlesinger LS. Pulmonary Surfactant Protein A inhibits macrophage reactive intermediate production in response to stimuli by reducing NADPH oxidase activity J. Immunol., 172:6866-6874, 2004.

Olakanmi O, Schlesinger LS, Ahmed A, Britigan BE. The nature of extracellular iron influences iron acquisition by Mycobacterium tuberculosis residing within human macrophages. Infect. Immun. 72:2022-2028, 2004.

Beharka AA, Crowther JE, McCormack FX, Denning G, Lees J, Tibesar E, Schlesinger LS.  Pulmonary Surfactant Protein A activates a PI3 Kinase / calcium signal transduction pathway in human macrophages: participation in the up-regulation of mannose receptor activity. J. Immunol. 175: 2227-2236, 2005

Kang PB, Azad AK, Torrelles JB, Kaufman TM, Beharka A, Tibesar E, Schlesinger LS. The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis J Exp. Med. 202:987-999, 2005.

McCarthy TR, Torrelles JB, MacFarlane A, Katawczik M, Kutzbach B, Clegg S, DesJardin LE, Goldberg JB, Schlesinger LS. Mycobacterium  tuberculosis manB, a phosphomannomutase that increases phosphatidylinositol mannoside biosynthesis in M. smegmatis and mycobacterial association with Human Macrophages. Mol. Micro. 58:774-790, 2005.

 Crowther JE and Schlesinger LS. Defining the phagocytic pathway for Surfactant Protein A in human macrophages: binding, clathrin-dependent Uptake, and trafficking through the endolysosomal pathway (in press, Am J Physiol.).