Graduate Student , University of Calgary
Human CD14+ monocyte-derived dendritic cells fail to process Cryptococcus gattii and activate T cell
INTRODUCTION: Cryptococcus gattii is a fungus that has recently appeared on Vancouver Island and Lower Mainland BC. The infection starts in the lung and causes devastating pneumonia and brain infections in otherwise healthy individuals, resulting in disability and even death. To date, more than 550 cases have occurred on Vancouver Island and the Pacific Northwest. The majority of these infections occur in patients with no identifiable immune suppression, and the mortality is more than 15%. This is a devastating illness, affecting people in the prime of their lives. It follows that the host immune system is critical for elimination of fungal pathogens such as C. gattii. However, it remains a mystery why otherwise healthy individuals are unable to defend themselves against C. gattii from the Vancouver Island Outbreak when they appear to mount an effective response to highly related organisms.
PROJECT OBJECTIVE: Based on preliminary results from experiments, we suspect that Vancouver Island Outbreak C. gattii sabotages recognition by our immune system by hiding inside the very cells than initiate effective immunity. The goal of this proposal is to define the nature of the induced immune defects. As an emerging and novel pathogen with devastating consequences, we need to understand the infection and the host response if we are to optimally prevent/ manage the lung infection, which is why we will work directly with primary human immune cells. Further, the work may enhance our understanding of why some people get infections and others do not, and potentially inform vaccine strategies.
Abstract: Cryptococcal infections are seen throughout the United States in both immunocompromised and immunocompetent patients. The most common form is C. neoformans. In the Northwestern United States, C. gattii has received considerable attention secondary to increased virulence resulting in significant morbidity and mortality. There are no cases in the extant literature describing a patient with C. gattii requiring neurosurgical intervention in Alabama. A middle-aged immunocompetent male with no recent travel or identifiable exposure presented with meningitis secondary to C. gattii. The patient underwent 12 lumbar punctures and a ventriculoperitoneal shunt and required 83 days of inpatient therapy with 5-flucytosine and amphotericin B. The patient was found to have multiple intracranial lesions and a large intramedullary spinal cryptococcoma within his conus. Following an almost 3-month hospitalization the patient required treatment with oral voriconazole for one year. In the United States meningitis caused by C. gattii infection is not isolated to the Northwestern region.
Pub.: 27 Dec '16, Pinned: 28 Jun '17
Abstract: Cryptococcosis is a major invasive fungal disease related worldwide with the AIDS population. New reports of HIV/AIDS cases to the national public health surveillance system (SIVIGILA) in Colombia have shown that there is a growing community at risk of contracting cryptococcosis throughout the country who do not have access to ART. Even though the most prevalent species Cryptococcus neoformans is mainly associated with the HIV population, we report a fatal case of cryptococcosis in an AIDS patient in Barranquilla, associated with Cryptococcus gattii VGI, isolated from blood culture.
Pub.: 08 Jun '17, Pinned: 28 Jun '17
Abstract: Cryptococcus gattii infection in mammals and birds has been confined historically to tropical and subtropical regions in Australia, Southeast Asia, Africa, and South America. Since the early 2000s, numerous reports describe the emergence of C. gattii on the Pacific Coast of North America. We report on a C. gattii infection in an 8-year-old male citron-crested cockatoo (Cacatua sulphurea citrinocristata) hatched on the Canadian Pacific Coast and raised in the province of Québec, Canada. The bird developed a slow growing ulcerated, fleshy, crusty, and hemorrhagic mass infiltrating the left lower rhamphotheca. Cryptococcus gattii infection was confirmed by cytologic examination of a fine needle aspirate of the mass, and results of fungal culture and sequencing. The genotype of the strain was determined to be VGIIa sequence type 20, the strongly overrepresented subgroup found on the Canadian Pacific coast. Minimum inhibitory concentrations for multiple antifungal drugs were determined. The bird received fluconazole but died acutely 55 days after initial presentation. Postmortem examination revealed a disseminated infection, with involvement of the beak, lungs, spleen, and brain.
Pub.: 24 Jun '17, Pinned: 28 Jun '17
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