Search

Your search keyword '"Wormley, Floyd L."' showing total 121 results
Start Over Author "Wormley, Floyd L." Search Limiters Full Text
121 results on '"Wormley, Floyd L."'

9. A Novel Mycovirus Evokes Transcriptional Rewiring in the Fungus Malassezia and Stimulates Beta Interferon Production in Macrophages

Author

Wormley, Floyd L, Wormley, F L ( Floyd L ), Applen Clancey, Shelly, Ruchti, Fiorella, LeibundGut-Landmann, Salomé; https://orcid.org/0000-0002-5724-4837, Heitman, Joseph, Ianiri, Giuseppe; https://orcid.org/0000-0002-3278-8678, Wormley, Floyd L, Wormley, F L ( Floyd L ), Applen Clancey, Shelly, Ruchti, Fiorella, LeibundGut-Landmann, Salomé; https://orcid.org/0000-0002-5724-4837, Heitman, Joseph, and Ianiri, Giuseppe; https://orcid.org/0000-0002-3278-8678

Abstract

Mycoviruses infect fungi, and while most persist asymptomatically, there are examples of mycoviruses having both beneficial and detrimental effects on their host. Virus-infected Saccharomyces and Ustilago strains exhibit a killer phenotype conferring a growth advantage over uninfected strains and other competing yeast species, whereas hypovirus-infected Cryphonectria parasitica displays defects in growth, sporulation, and virulence. In this study, we identify a double-stranded RNA (dsRNA) mycovirus in five Malassezia species. Sequence analysis reveals it to be a totivirus with two dsRNA segments: a larger 4.5-kb segment with genes encoding components for viral replication and maintenance, and a smaller 1.4-kb segment encoding a novel protein. Furthermore, transcriptome sequencing (RNA-seq) of virus-infected versus virus-cured Malassezia sympodialis revealed an upregulation of dozens of ribosomal components in the cell, suggesting the virus modifies the transcriptional and translational landscapes of the cell. Given that Malassezia is the most abundant fungus on human skin, we assessed the impact of the mycovirus in a murine epicutaneous infection model. Although infection with virus-infected strains was not associated with an increased inflammatory response, we did observe enhanced skin colonization in one of two virus-infected M. sympodialis strains. Noteworthy, beta interferon expression was significantly upregulated in bone marrow-derived macrophages when challenged with virus-infected, compared to virus-cured, M. sympodialis, suggesting that the presence of the virus can induce an immunological response. Although many recent studies have illuminated how widespread mycoviruses are, there are relatively few in-depth studies about their impact on disease caused by the host fungus. We describe here a novel mycovirus in Malassezia and its possible implications in pathogenicity.

Published
2020

10. Depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased IL-17A production by gamma/delta T cells

Author

Wozniak Karen L, Kolls Jay K, and Wormley Floyd L

Subjects
Gamma-delta T cells, Cryptococcus neoformans, IL-17A, Pulmonary, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Protective responses in mice immunized with an interferon-gamma producing strain of Cryptococcus neoformans, H99γ, are associated with IL-17A production by neutrophils. Neutrophil depletion in H99γ-immunized mice did not affect pulmonary fungal burden, indicating that neutrophils are not required for clearance. However, we observed an increase in IL-17A in the lungs of neutrophil-depleted H99γ infected mice, which corresponded to an increase in IL-17A+ γδ+ T cells. Moreover, we observed increased IL-17A+/ CD3+ cells and IL-17A+/γδ+ cells, but decreased IL-17A+/Ly6G+ neutrophils in the lungs of IL-17 receptor (R)A deficient mice compared to wild-type mice. Increased production of IL-17A in neutropenic mice coincided with increased IL-6 and CXCL1, but not Th17 inducing cytokines TGF-β, IL-21 and IL-23. Concurrent depletion of neutrophils and γδ+ T cells reduced IL-17A levels. Our results suggest that γδ+ T cells mediate significant IL-17A production in neutropenic mice during the protective response to C. neoformans infection.

Published
2012
Full Text
View/download PDF

14. Th1/Th2 cytokine expression in saliva of HIV-positive and HIV-negative individuals: a pilot study in HIV-positive individuals with oropharyngeal candidiasis

Author

Leigh, Janet E., Steele, Chad, Wormley, Floyd L., Jr., Luo, Wei, Clark, Rebecca A., Gallaher, William, and Fidel, Paul L., Jr.

Subjects
Cytokines -- Physiological aspects, HIV infection -- Physiological aspects, Thrush (Mouth disease) -- Physiological aspects, Health
Abstract

The expression of Th2 cytokines in oral mucosa may predict which HIV patients might develop oral candidiasis. Th2 cytokines include interleukin-4 and interleukin-10 whereas Th1 cytokines include interleukin-2 and interferon gamma. Researchers analyzed saliva samples from 20 HIV-positive people and 25 HIV-negative people. The HIV-negative group had both Th1 and Th2 cytokines in equal proportions. The HIV-positive group had a predominance of Th2 cytokines, which seemed to be a result of a lack of Th1 cytokines. Those with oral candidiasis had an even greater excess of Th2 cytokines.

Published
1998

28. Repurposing auranofin as an antifungal: In vitro activity against a variety of medically important fungi.

Author

Wiederhold, Nathan P., Patterson, Thomas F., Srinivasan, Anand, Chaturvedi, Ashok K., Fothergill, Annette W., Wormley, Floyd L., Ramasubramanian, Anand K., and Lopez-Ribot, José L.

Subjects
AURANOFIN, ANTIFUNGAL agents, COMMUNICABLE disease treatment, MYCOSES, RHEUMATOID arthritis treatment, CANDIDA albicans
Abstract

Repositioning old drugs can significantly decrease the time and effort that it takes to develop novel antifungal therapeutics, which represents a pressing and unmet clinical need due to the devastating nature of fungal infections. We have previously described the activity of auranofin, a gold thiol compound used to treat rheumatoid arthritis, againstCandida albicansbiofilms. Here we evaluate its antifungal spectrum of action and describe its activity against a variety of medically important fungi. [ABSTRACT FROM PUBLISHER]

Published
2017
Full Text
View/download PDF

34. Repurposing auranofin as an antifungal: In vitroactivity against a variety of medically important fungi

Author

Wiederhold, Nathan P., Patterson, Thomas F., Srinivasan, Anand, Chaturvedi, Ashok K., Fothergill, Annette W., Wormley, Floyd L., Ramasubramanian, Anand K., and Lopez-Ribot, José L.

Abstract

ABSTRACTRepositioning old drugs can significantly decrease the time and effort that it takes to develop novel antifungal therapeutics, which represents a pressing and unmet clinical need due to the devastating nature of fungal infections. We have previously described the activity of auranofin, a gold thiol compound used to treat rheumatoid arthritis, against Candida albicansbiofilms. Here we evaluate its antifungal spectrum of action and describe its activity against a variety of medically important fungi.

Published
2017
Full Text
View/download PDF

47. Antifungal Activity of Plasmacytoid Dendritic Cells against Cryptococcus neoformansIn VitroRequires Expression of Dectin-3 (CLEC4D) and Reactive Oxygen Species

Author

Hole, Camaron R., Leopold Wager, Chrissy M., Mendiola, Andrew S., Wozniak, Karen L., Campuzano, Althea, Lin, Xin, and Wormley, Floyd L.

Abstract

ABSTRACTConventional dendritic cells (cDCs) are critical for protection against pulmonary infection with the opportunistic fungal pathogen Cryptococcus neoformans; however, the role of plasmacytoid dendritic cells (pDCs) is unknown. We show for the first time that murine pDCs have direct activity against C. neoformansvia reactive oxygen species (ROS), a mechanism different from that employed to control Aspergillus fumigatusinfections. The anticryptococcal activity of murine pDCs is independent of opsonization but appears to require the C-type lectin receptor Dectin-3, a receptor not previously evaluated during cryptococcal infections. Human pDCs can also inhibit cryptococcal growth by a mechanism similar to that of murine pDCs. Experimental pulmonary infection of mice with a C. neoformansstrain that induces protective immunity demonstrated that recruitment of pDCs to the lungs is CXCR3 dependent. Taken together, our results show that pDCs inhibit C. neoformansgrowth in vitrovia the production of ROS and that Dectin-3 is required for optimal growth-inhibitory activity.

Published
2016
Full Text
View/download PDF

48. Pulmonary Infection with an Interferon-γ-Producing Cryptococcus neoformansStrain Results in Classical Macrophage Activation and Protection

Author

Hardison, Sarah E., Ravi, Sailatha, Wozniak, Karen L., Young, Mattie L., Olszewski, Michal A., and Wormley, Floyd L.

Abstract

Alternative macrophage activation is associated with exacerbated disease in murine models of pulmonary cryptococcosis. The present study evaluated the efficacy of interferon-γ transgene expression by Cryptococcus neoformansstrain H99γ in abrogating alternative macrophage activation in infected mice. Macrophage recruitment into the lungs of mice after infection with C. neoformansstrain H99γ was comparable with that observed in mice challenged with wild-type C. neoformans. However, pulmonary infection in mice with C. neoformansstrain H99γ was associated with reduced pulmonary fungal burden, increased pulmonary Th1-type and interleukin-17 cytokine production, and classical macrophage activation as evidenced by increased inducible nitric oxide synthase expression, histological evidence of enhanced macrophage fungicidal activity, and resolution of inflammation. In contrast, progressive pulmonary infection, enhanced Th2-type cytokine production, and the induction of alternatively activated macrophages expressing arginase-1, found in inflammatory zone 1, Ym1, and macrophage mannose receptor were observed in the lungs of mice infected with wild-type C. neoformans. These alternatively activated macrophages were also shown to harbor highly encapsulated, replicating cryptococci. Our results demonstrate that pulmonary infection with C. neoformansstrain H99γ results in the induction of classically activated macrophages and promotes fungal clearance. These studies indicate that phenotype, as opposed to quantity, of infiltrating macrophages correlates with protection against pulmonary C. neoformansinfection.

Published
2010
Full Text
View/download PDF

49. Calcineurin Is Essential for Candida albicansSurvival in Serum and Virulence

Author

Blankenship, Jill R., Wormley, Floyd L., Boyce, Molly K., Schell, Wiley A., Filler, Scott G., Perfect, John R., and Heitman, Joseph

Abstract

ABSTRACTCalcineurin is a calcium-activated protein phosphatase that is the target of the immunosuppressants cyclosporin A and FK506. In T cells, calcineurin controls nuclear import of the NF-AT transcription factor and gene activation. In plants and fungi, calcineurin functions in stress responses (e.g., temperature, cations, and pH) and is necessary for the virulence of the fungal pathogen Cryptococcus neoformans. Here we show that calcineurin is also required for the virulence of another major fungus that is pathogenic to humans, Candida albicans. C. albicanscalcineurin mutants had significantly reduced virulence in a murine model of systemic infection. In contrast to its role in C. neoformans, calcineurin was not required for C. albicanssurvival at 37°C. Moreover, C. albicanscalcineurin mutant strains exhibited no defects in known Candidavirulence traits associated with host invasion, including filamentous growth, germ tube formation, and adherence to and injury of mammalian cells. C. albicanscalcineurin mutant strains failed to colonize and grow in the kidneys of infected animals and were unable to survive when exposed to serum in vitro. Our studies illustrate that calcineurin has evolved to control aspects of the virulence of two divergent fungal pathogens via distinct mechanisms that can be targeted to achieve broad-spectrum antifungal action.

Published
2003
Full Text
View/download PDF

50. Chlamydia trachomatisInfection Does Not Enhance Local Cellular Immunity against Concurrent CandidaVaginal Infection

Author

Kelly, Kathleen A., Gray, Heather L., Walker, Jennifer C., Rank, Roger G., Wormley, Floyd L., and Fidel, Paul L.

Abstract

ABSTRACTAlthough Th1-type cell-mediated immunity (CMI) is the predominant host defense mechanism against mucosal Candida albicansinfection, CMI against a vaginal C. albicansinfection in mice is limited at the vaginal mucosa despite a strongCandida-specific Th1-type response in the draining lymph nodes. In contrast, Th1-type CMI is highly effective against an experimental Chlamydia trachomatisgenital tract infection. This study demonstrated through two independent designs that a concurrent Candidaand Chlamydiainfection could not accelerate or modulate the anti-CandidaCMI response. Together, these results suggest that host responses to these genital tract infections are independent and not influenced by the presence of the other.

Published
2001
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results