Immunology & Infectious Diseases

George Deepe

George Deepe, MD

Int Med-Infect Disease

Professor

Research Summary

Histoplasma capsulatum is a dimorphic, pathogenic fungus that is endemic to the Ohio and Mississippi river valleys. Approximately, 200,000 to 500,000 new infections occur annually. Infection is initiated via inhalation of conidia and mycelia fragments that convert to yeast cells within mammalian tissues. The spectrum of disease ranges from an influenza-like illness to a chronic cavitary pulmonary disease to a progressive, disseminated form that is life-threatening. Individuals who require immunosuppressive drugs or who have advanced human immunodeficiency virus infection are at high risk for developing disseminated histoplasmosis. Successful resolution of infection requires a collaboration between T cells and macrophages. The research in Dr. George Deepe’s laboratory focuses on the contribution of T cells to clearance of the fungus. Specifically, the research projects are designed to ask questions regarding basic mechanisms by which T cells promote elimination of H. capsulatum, how they modify the inflammatory response to the fungus and identifying antigens that modulate the protective immune response.

The laboratory has several projects underway. One is centered on the identification of antigens from the fungus that elicit a protective immune response. Three antigens have been cloned and expressed, one of which, heat shock protein 60, does mediate protective immunity when as a vaccine. Dr. Deepe has mapped a region of the protein which contains the protective domain. Subsequent studies will endeavor to identify the smallest fragment that can elicit protective immunity and the T cell receptor repertoire of T cells engaged by the protective epitope. Thus, Dr. Deepe can begin to understand at the T cell receptor level, which family or families of T cells are key in clearance.

The second major project is delineation of the cytokine networks involved in protective immunity and exacerbation. The specific focus is on those cytokines that are released in lungs of mice infected with yeast cells, and their role in modulating the host response. Dr. Deepe has demonstrated that interleukin-12 and tumor necrosis factor-a are critically important for survival of naive mice infected with the fungus, whereas the latter cytokine is much more important in reexposure disease. The third major project is an examination of the T cell receptor repertoire in the lungs of mice infected with H. capsulatum to determine if there is a bias in the T cell receptor usage and if that bias provides clues to which T cell families are important in host clearance.

Dr. Deepe is a well-recognized leader in the cellular immunology of fungal infections. His specific research interests involve characterization of the protective T-cell epitopes of H. capsulatum antigens and analysis of the functional activity of antigen-reactive T-cells. He is board certified in both internal medicine and infectious diseases. Dr. Deepe's published works include approximately 100 original publications and 36 abstracts. He has been elected to membership in the Association of American Physicians, American Society for Microbiology, The American Association for the Advancement of Science, American College of Physicians, American Federation for Clinical Research, International Society for Human and Animal Mycology, American Association of Immunologists, Central Society for Clinical Research and a Fellow in the Infectious Diseases Society of America. Dr. Deepe is a member of the editorial board of infection and immunity and a reviewer for Infection and Immunity, Journal of Immunology, Journal of Leukocyte Biology, Journal of Infectious Diseases, Journal of Clinical Investigation and Clinical Infectious Diseases.

Recent Publications

Szymczak WA, Deepe GS Jr. The CCL7-CCL2-CCR2 axis regulates IL-4 production inlungs and fungal immunity. J Immunol. 2009 Aug 1;183(3):1964-74. Epub 2009 Jul 8.PubMed PMID: 19587014.

Deepe GS Jr, Gibbons RS. Interleukins 17 and 23 influence the host response toHistoplasma capsulatum. J Infect Dis. 2009 Jul 1;200(1):142-51. PubMed PMID:19469707; PubMed Central PMCID: PMC2715335.

Winters MS, Spellman DS, Chan Q, Gomez FJ, Hernandez M, Catron B, Smulian AG, Neubert TA, Deepe GS Jr. Histoplasma capsulatum proteome response to decreasediron availability. Proteome Sci. 2008 Dec 24;6:36. PubMed PMID: 19108728; PubMed Central PMCID: PMC2645362.

Deepe GS Jr, Gibbons RS, Smulian AG. Histoplasma capsulatum manifestspreferential invasion of phagocytic subpopulations in murine lungs. J LeukocBiol. 2008 Sep;84(3):669-78. Epub 2008 Jun 24. PubMed PMID: 18577715; PubMedCentral PMCID: PMC2516902. 

Deepe GS Jr, Gibbons RS. TNF-alpha antagonism generates a population ofantigen-specific CD4+CD25+ T cells that inhibit protective immunity in murinehistoplasmosis. J Immunol. 2008 Jan 15;180(2):1088-97. PubMed PMID: 18178849;PubMed Central PMCID: PMC2447823.

Smulian AG, Gibbons RS, Demland JA, Spaulding DT, Deepe GS Jr. Expression ofhygromycin phosphotransferase alters virulence of Histoplasma capsulatum.Eukaryot Cell. 2007 Nov;6(11):2066-71. Epub 2007 Sep 14. PubMed PMID: 17873086;PubMed Central PMCID: PMC2168422.

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