Training:
•
Undergraduate: Brown University, B.A. in Biology, Magna Cum Laude, 1974
•
Graduate: Georgetown University, M.D., Cum Laude, 1978
•
Postdoctoral: Combined internship and residency in Internal Medicine and
Pediatrics, University of North Carolina, Chapel Hill, 1978 to 1982
• Adult and Pediatric Infectious Diseases, University of North Carolina,
Chapel Hill, 1984 to 1987; trained with Dr. Janne Cannon, Department of
Microbiology and Immunology
Summary of the focus of the research of Dr. Spinola:
The Spinola laboratory focuses on the pathogenesis of and host response to the bacterium Haemophilus ducreyi in an experimental model of human infection.
Description and summary of research focus of the laboratory:
Our research focuses on the pathogenesis of and human immune response to Haemophilus ducreyi, the etiologic agent of the genital ulcer disease chancroid, a cofactor in the transmission of HIV-1. We developed a human infection model in which volunteers are inoculated on the skin of the arm with H. ducreyi . Features of the model include a low estimated dose required for infection (1 to 100 cfu), a clinical course that resembles the papular and pustular stages of naturally occurring disease, a cutaneous immune response that consists of an abscess of polymorphonuclear leukocytes, a macrophage collar and a collection of dermal T cells that resemble a poorly formed granuloma. In confocal microscopy, the bacteria co-localize neutrophils and macrophages but remain extracellular throughout experimental infection. The histology of an abscess and a granuloma is unusual for an extracellular pathogen, and suggests H. ducreyi is causing immune dysregulation. We have found that there are gender and host effects on susceptibility to disease progression, and we are examining whether the interaction of H. ducreyi with dendritic cells may cause a tolerizing response that leads to phagocytic failure in people who form pustules. We are also interested in understanding how H. ducreyi promotes HIV-acquisition and have characterized expression of chemokines and chemokine receptors responsible for T cell and macrophage recruitment. Another focus of the laboratory is to capture bacterial transcripts that are upregulated during infection of the human host. Putative virulence determinants in the pathogenesis of infection are evaluated by testing isogenic mutants in human volunteers. Trainees may work on any of these projects and will be exposed to molecular biology, immunology, cell biology and the methods and ethics of human research.
Publications
Spinola SM, Bauer ME, and Munson RS. Immunopathogenesis of Haemophilus ducreyi infection (chancroid). Infect. Immun. 2002; 70 :1667-1676.
Humphreys TL, Schnizlein-Bick CT, Katz BP, Baldridge LA, Hood AF, Hromas RA, and Spinola SM. Evolution of the cutaneous immune response to experimental Haemophilus ducreyi infection and its relevance to HIV-1 acquisition. J. Immunology. 2002; 169 :6316-6323.
Soler D, Humphreys TL, Spinola SM, and Campbell JJ. CCR4 versus CCR10 in human cutaneous T H lymphocyte trafficking. Blood. 2003; 101 :1677-1683.
Spinola SM, Bong CTH, Faber A, Fortney KR, Bennett S, Townsend C, Zwickl B, Billings SD, Humphreys TL, Bauer ME, and Katz BP. Differences in host susceptibility to disease progression in the human challenge model of Haemophilus ducreyi infection. Infect. Immun. 2003; 71 :6658-6663.
Janowicz DM, Fortney KR, Katz BP, Latimer JL, Deng K, Hansen EJ, and Spinola SM. Expression of the LspA1 and LspA2 proteins by Haemophilus ducreyi is required for virulence in human volunteers. Infect. Immun. 2004; 72 :4528-4533.
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