1574. Identification of Host-Derived Biomarker Signatures in Cryptococcal Infection
Session: Poster Abstract Session: Mycology: Diagnostic
Friday, October 28, 2016
Room: Poster Hall
Posters
  • Holcomb Cryptococcus Poster-compressed.pdf (907.9 kB)
  • Background: Cryptococcal species cause invasive fungal infections capable of producing life-threating complications, including pulmonary disease and meningoencephalitis. Understanding of the pathogenesis of disease and the host response to infection is still limited. We report the first peripheral blood gene expression analysis of the host response to infection with Cryptococcus neoformans (C. neoformans) and Cryptococcus gattii (C. gattii).

    Methods: Forty-five BALB/cJ mice were challenged intranasally with C. neoformans, C. gattii, or sham control. The mice were followed serially and sacrificed 14 days post-infection. Whole blood was collected for transcriptomic analysis, along with various tissues to examine fungal burden. Differential gene expression was analyzed using Affymetrix microarrays. Functional gene expression pathway analysis was examined using gene set enrichment analysis, Ingenuity Pathway Analysis (IPA), and the Database for Annotation, Visualization, and Integrated Discovery (DAVID).

    Results: The host peripheral blood transcriptomic response to C. neoformans was more robust than the response to C. gattii on the transcriptomic level, and mice infected with C. neoformans exhibited significantly higher organism burden in brain, lung, and splenic tissues. Significantly up-regulated genes in the infected mice clustered primarily into immune function pathways, including up-regulation of complement activity, skewing toward TH2-mediated immunity, and alternative activation of macrophages.

    Conclusion: Transcriptomic analysis demonstrates differences in both the character and magnitude of the host response to C. neoformans and C. gattii and provides insight into the mechanistic nature of these different host responses. The host response to these organisms, as measured by gene expression in circulating white blood cells, proves useful both for improving our understanding of the unique pathophysiology of these infections, as well as potentially contributing to the development of future diagnostic assays based on gene-expression based biomarkers.

    Zachary Holcomb, BS1, Aimee Zaas, MD, MHS1, Marisol Betancourt-Quiroz, MS1, John Perfect, MD, FIDSA2 and Micah T. Mcclain, MD, PhD3, (1)Duke University Medical Center, Durham, NC, (2)Medicine, Duke University School of Medicine, Durham, NC, (3)Internal Medicine/Division of Infectious Diseases, Duke University Medical Center, Durham, NC

    Disclosures:

    Z. Holcomb, None

    A. Zaas, None

    M. Betancourt-Quiroz, None

    J. Perfect, None

    M. T. Mcclain, None

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