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The pathogenesis of experimental Emergomycosis in mice

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posted on 2024-04-15, 10:06 authored by Maxine A. Höft, Lucian Duvenage, Sumayah Salie, Roanne KeetonRoanne Keeton, Alfred Botha, Ilan S. Schwartz, Professor Nelesh P. Govender, Gordon D Brown, Jennifer Claire Hoving

Emergomyces africanus is a recently identified thermally-dimorphic fungal pathogen that causes disseminated infection in people living with advanced HIV disease. Known as emergomycosis, this disseminated disease is associated with very high case fatality rates. Over the last decade, improved diagnostics and fungal identification in South Africa resulted in a dramatic increase in the number of reported cases. Although the true burden of disease is still unknown, emergomycosis is among the most frequently diagnosed dimorphic fungal infections in Southern Africa; and additional species in the genus have been identified on four continents. Little is known about the pathogenesis and the host’s immune response to this emerging pathogen. Therefore, we established a murine model of pulmonary infection using a clinical isolate, E. africanus (CBS 136260). Both conidia and yeast forms caused pulmonary and disseminated infection in mice with organisms isolated in culture from lung, spleen, liver, and kidney. Wild-type C57BL/6 mice demonstrated a drop in body weight at two weeks post-infection, corresponding to a peak in fungal burden in the lung, spleen, liver, and kidney. An increase in pro-inflammatory cytokine production was detected in homogenized lung supernatants including IFN-γ, IL-1β, IL-6, IL12-p40 and IL-17 at three- and four-weeks post-infection. No significant differences in TNF, IL-12p70 and IL-10 were observed in wild-type mice between one and four-weeks post-infection. Rag-1-deficient mice, lacking mature T-and B-cells, had an increased fungal burden associated with reduced IFN-γ production. Together our data support a protective T-helper type-1 immune response to E. africanus infection. This may provide a possible explanation for the susceptibility of only a subset of people living with advanced HIV disease despite hypothesized widespread environmental exposure. In summary, we have established a novel murine model of E. africanus disease providing critical insights into the host immune components required for eliminating the infection.

Funding

National Research Foundation of South Africa

History

Publisher

Stellenbosch University

Contributor

Höft, Maxine A.; Duvenage, Lucian; Salie, Sumayah; Keeton, Roanne; Botha, Alfred; Schwartz, Ilan S.; Govender, Nelesh P. Brown, Gordon D.; & Hoving, Jennifer C.

Date

2024-01-10

Format

.pdf .tiff .png .ppt

Language

en

Geographical Location

South Africa, Cape Town

Academic Group

  • Medicine and Health Sciences

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Recommended Citation

Höft, MA, Duvenage, L, Salie, S, Keeton, R, Botha, A, Schwartz, IS, Govender, NP, Brown, GD & Hoving, JC. 2024. The pathogenesis of experimental Emergomycosis in mice. Stellenbosch University. Dataset. DOI: https://doi.org/10.25413/sun.25604127

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