Larry Schlesinger, MD 

Because tuberculosis continues to cause worldwide morbidity and mortality, the laboratory of Larry Schlesinger, MD, professor of Internal Medicine and director of the OSU Division of Infectious Diseases, strives to understand components of the human immune system that regulate the body’s response during primary infection in the lung by Mycobacterium tuberculosis.

Specifically, Schlesinger and colleagues focus on biological interactions that mediate recognition and intracellular trafficking of M. tuberculosis in human macrophages (white blood cells that normally kill micro-organisms), the role of complement and lung surfactant (surface material), and the role of M. tuberculosis cell wall components in these processes. Schlesinger’s recent work examines pulmonary models of the innate immune response to tuberculosis and non-tuberculosis mycobacteria, the use of current molecular approaches to making knock-out strains of bacteria, and iron metabolism in M. tuberculosis-infected macrophages.

In a 2004 study published in the Journal of Immunology, Schlesinger and colleagues reported on the process by which host defense cells called alveolar macrophages continuously consume invading environmental and infectious particles. The team examined the effects of a lung surfactant protein called SP-A – which has been shown to alter macrophage immune functions – on the oxidative response of human macrophages to particulate stimuli.

Their study demonstrated that SP-A inhibits damaging macrophage reactive oxygen intermediate (ROI) production in response to these stimuli by reducing oxidase activity. This finding, they wrote, “supports an anti-inflammatory role for SP-A in pulmonary homeostasis (equilibrium) by inhibiting macrophage production of ROI through a reduction in…oxidase activity.” It also offers a clue for how the lung stays healthy despite inhaling microbes daily and could lead to new therapeutic approaches. 

Schlesinger, holder of the Saslaw Professorship in Infectious Diseases, also directs the Center for Microbial Interface Biology (CMIB) at OSU, a new interdisciplinary program devoted to research on infectious diseases, pathogenesis and bioterrorism. The CMIB collaborates with investigators from across the OSU campus in immunology, cell biology, pathology, biochemistry and pharmacology, microbiology, genetics, structural biology and bioinformatics.

“Microbial pathogens encompass bacteria, viruses, fungi and parasites, which collectively account for a large percentage of human disease,” Schlesinger says. “Answering fundamental questions about host-microbe interactions requires a multidisciplinary approach. Through the CMIB, we take just such an approach.”

Dr. Schlesinger’s co-investigators include: Periannan Kuppusamy, PhD; Vijay Kutala, PhD; and Jay Zweier, MD. His collaborative team of OSU researchers includes: Abul Azad, PhD; John Gunn, PhD; Bradford McGwire, MD, PhD; Robert Munson, PhD; Joanne Turner, PhD; and Mark Wewers, MD.