Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Sep;3(9):416-423.
doi: 10.1128/microbe.3.416.1.

Insights into Fungal Morphogenesis and Immune Evasion: Fungal conidia, when situated in mammalian lungs, may switch from mold to pathogenic yeasts or spore-forming spherules

Greg Gauthier  1 , Bruce S Klein
Affiliations

Insights into Fungal Morphogenesis and Immune Evasion: Fungal conidia, when situated in mammalian lungs, may switch from mold to pathogenic yeasts or spore-forming spherules

Greg Gauthier et al. Microbe Wash DC. 2008 Sep.
No abstract available

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Morphologic forms of the endemic dimorphic fungi. The mold form of each organism is on the left and the yeast or spherule form is on the right are depicted. The infectious particles acquired from the environment are shown on the left and tissue-based form on the right. One exception is the tuberculate macroconidia of Histoplasma, which is not believed to be the infectious particle. Microscopic images were provided by Garry Cole (Coccidiodes); George Deepe and George Smulian (Histoplasma); Gustavo Goldman (Paracoccidiodes); Chester Cooper (Penicillium); and Nuri Rodriguez (Sporothrix).
FIGURE 2
FIGURE 2
High-osmolarity glycerol (HOG) pathway in S. cerevisiae, C. albicans, and C. neoformans. (A) Sln1 undergoes autophosphorylation in the absence of osmotic, oxidative, or temperature stress. This phosphate is transferred to a phosphotransfer protein, Ypd1, which relays it to and inactivates the response regulator protein, Ssk1. The presence of osmotic, oxidative, or temperature (heat or cold) stress, inhibits the phosphorelay between Sln1, Ypd1, and Ssk1, resulting in unphosphorylated and active Skk1, which can then interact with Ssk2/22. This interaction promotes Ssk2/22 autophosphorylation, which triggers the MAPK cascade resulting in phosphorylation of Pbs2 and Hog1. Phosphorylated Hog1 translocates from the cytoplasm to the nucleus to activate transcription factors involved with osmoadaption, resistance to oxidative stress, and thermal tolerance. (B) The phosphorelay between Sln1, Ypd1, Ssk1 and activation of the MAPK cascade in the human pathogen C. albicans is postulated to be similar to that in S. cerevisiae. Phosphorylated Hog1 translocates from the cytoplasm to the nucleus to activate transcription factors that contribute to C. albicans adaptation and resistance to osmotic, oxidative, and temperature stress, as well as UV irradiation. In addition to Sln1, there is an unknown osmotic stress response pathway that bypasses Ssk1. (C) In the absence of environmental stress, C. neoformans Hog1 is constitutively phosphorylated. This has been demonstrated in most, but not all, C. neoformans isolates. Phosphorylated Hog1 negatively regulates pheromone production, capsule formation, and melanin biosynthesis. In the presence of osmotic, oxidative, and temperature stress, as well as UV irradiation, Hog1 becomes dephosphorylated by the action of phosphatases facilitating C. neoformans adaptation to these stresses. It is unknown if the regulation of the phosphorelay between Tco1/2, Ypd1, and Ssk1 is similar to S. cerevisiae. (Figure adapted with permission from Bahn YS et al., Nature Rev. Microbiol.5:57–69, 2007).
FIGURE 3
FIGURE 3
Selected mechanisms of immune evasion in B. dermatitidis and H. capsulatum. (A) Blastomyces BAD1 downregulates TNF-α production by phagocytes. Yeast surface BAD1 binds to CR3 and CD14 receptors on macrophages and neutrophils stimulating the production of TGF-β, which acts in an autocrine and paracrine fashion to inhibit TNF-α production. Soluble BAD1 also binds CR3, facilitating receptor-mediated endocytosis. Internalized BAD1 is postulated to alter intracellular signaling to inhibit TNF-α production. (B) Histoplasma α-(1,3)-glucan blocks dectin-1 recognition of β-glucan. H. capsulatum α-(1,3)-glucan shields β-(1,3)-glucan in the cell wall from phagocyte Dectin-1 receptor recognition. The absence of α-(1,3)-glucan in the H. capsulatum cell wall leaves β-(1,3)-glucan exposed and accessible for phagocyte recognition and binding by Dectin-1 receptors. Engagement of the Dectin-1 receptor promotes phagocytosis, generation of the respiratory burst, and activation of NF-κB resulting in TNF-α and interleukin (IL-2, IL-6, IL-10, IL-12) production.
See this image and copyright information in PMC

References

    1. Brandhorst TT, Wuthrich M, Finkel-Jimenez B, Warner T, Klein BS. Exploiting type 3 complement receptor for TNF-alpha suppression, immune evasion, and progressive pulmonary infection. J. Immunol. 2004;173:7444–7453. - PubMed
    1. Hung CY, Yu JJ, Seshan KR, Reichard U, Cole GT. A parasitic phase-specific adhesion of Coccidioides immitis contributes to the virulence of this respiratory fungal pathogen. Infect. Immun. 2002;70:3443–3456. - PMC - PubMed
    1. Hung CY, Seshan KR, Yu JJ, Schaller R, Xue J, Basrur V, Gardner MJ, Cole GT. A metalloproteinase of Coccidioides posadasii contributes to evasion of host detection. Infect. Immun. 2005;73:6689–6703. - PMC - PubMed
    1. Koneti A, Linke MJ, Brummer E, Stevens DA. Evasion of innate immune responses: evidence for mannose binding lectin inhibition of TNF-α production by macrophages in response to Blastomyces dermatitidis. Infect. Immun. 2008;76:994–1002. - PMC - PubMed
    1. Maresca B, Kobayashi GS. Changes in membrane fluidity modulate heat shock gene expression and produced attenuated strains in the dimorphic fungus H. capsulatum. Arch. Med. Res. 1993;24:247–249. - PubMed

LinkOut - more resources