George Deepe, MD
Int Med-Infect Disease
MSB 7163
P. O. Box 670560
Cincinnati OH 45267
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 Deepeā€™s laboratory focuses on the collaboration between soluble mediators and cellular effectors in clearance of the fungus. Specifically, the research projects are designed to ask questions regarding basic mechanisms by which myeloid cells or T cells promote elimination of H. capsulatum and how they modify the inflammatory response to the fungus.

The laboratory has several projects underway. One is centered on the influence of nutritional immunity and control of Histoplasma infection. We have shown that activation of macrophages with the cytokine graunulocyte-macrophage colony stimulating factor (GM-CSF) restricts the growth of this fungus in macrophages. This cytokine induces growth limitation by starving the organism of trace metal zinc. We are investigating how zinc is withheld from the organism and how it is transported from the phagosome to the cytosol.

A second major project is delineation of the chemokine/cytokine networks involved in protective immunity and exacerbation. The specific focus is on those chemokines and cytokines that are released in lungs of mice infected with yeast cells, and their role in modulating the host response. For example mice lacking a chemokine receptor, CCR2, are much more susceptible to infection largely through the induction of interleukin-4 which dampens immunity. We are interested in the mechanisms that prompt production of interleukin-4 and how it exacerbates infection. In contrast, mice lacking the chemokine receptor CCR5 manifest an accelerated clearance of the fungus largely by increasing the production of IL-17. Studies that seek to decipher why IL-17 is enhanced in the absence of chemokine signaling and how it impacts the progress of infection are being undertaken. In addition, we are examining the influence of specific transcription factors such as Kruppel-like factor 2 on the myeloid response to Histoplasma.

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.

Selected Publications
Kroetz DN, and Deepe, Jr. GS. An aberrant thymus in CCR5-/- mice is coupled with an enhanced adaptive immune response to fungal infection. J. Immunol. 186:5949-5955, 2011.
Szymczak WS, and Deepe, Jr. GS. Antigen presenting dendritic cells rescue CD4-depleted CCR2-/- mice from lethal Histoplasma capsulatum infection. Infect. Immun. 78:2125-2137, 2010 (Spotlighted manuscript).
Kroetz DN, and Deepe, Jr. GS. CCR5 dictates the equilibrium of proinflammatory IL-17+ and regulatory Foxp3+ T cells in fungal infection. J. Immunol. 184:5224-5231, 2010.
Winters MS, Chan Q, Caruso JA, and Deepe, Jr. GS. Metallomic analysis of macrophages infected with Histoplasma capsulatum reveals a fundamental role for Zn in host defenses. J. Infect. Dis. 202:1136-1145, 2010.
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.