ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Cryptococcal heat shock protein 70 homolog Ssa1 contributes to pulmonary expansion of Cryptococcus neoformans during the afferent phase of the immune response by promoting macrophage M2 polarization.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Heat Shock Proteins in Medically Relevant Fungal Pathogens: From Molecular Chaperones to Virulence Factors and Therapeutic Targets.Journal of fungi (Basel, Switzerland) · 2026Review
- Advances in cryptococcal infections-associated immunopathology and potential therapeutic strategies.Frontiers in pharmacology · 2026Review
- Multi-Omics Analyses Reveal the Antifungal Mechanism of Phenazine-1-Carboxylic Acid AgainstJournal of fungi (Basel, Switzerland) · 2025Article
- Reduced growth and biofilm formation at high temperatures contribute to Cryptococcus deneoformans dermatotropism.Disease models & mechanisms · 2025Article
- Virulence factors released by extracellular vesicles fromFrontiers in cellular and infection microbiology · 2025Review
- Elements of dissemination in cryptococcosis.mBio · 2024Review
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- Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections.Microorganisms · 2023Review
- Non-self glycan structures as possible modulators of cancer progression: would polysaccharides from Cryptococcus spp. impact this phenomenon?Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Review
- PersistingFrontiers in cellular and infection microbiology · 2023Article
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- Review
- Alternative Splicing of Heat Shock Transcription Factor 2 Regulates the Expression of Laccase Gene Family in Response to Copper inApplied and environmental microbiology · 2021Article
- Chaperone Networks in Fungal Pathogens of Humans.Journal of fungi (Basel, Switzerland) · 2021Review
- Identification of Disease-Associated Cryptococcal Proteins Reactive With Serum IgG From Cryptococcal Meningitis Patients.Frontiers in immunology · 2021Article
- The Effect ofInfection and drug resistance · 2021Article
- Transcriptomic analysis reveals that mTOR pathway can be modulated in macrophage cells by the presence of cryptococcal cells.Genetics and molecular biology · 2021Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Numerous virulence factors expressed by Cryptococcus neoformans modulate host defenses by promoting nonprotective Th2-biased adaptive immune responses. Prior studies demonstrate that the heat shock protein 70 homolog, Ssa1, significantly contributes to serotype D C. neoformans virulence through the induction of laccase, a Th2-skewing and CNS tropic factor. In the present study, we sought to determine whether Ssa1 modulates host defenses in mice infected with a highly virulent serotype A strain of C. neoformans (H99). To investigate this, we assessed pulmonary fungal growth, CNS dissemination, and survival in mice infected with either H99, an SSA1-deleted H99 strain (Δssa1), and a complement strain with restored SSA1 expression (Δssa1::SSA1). Mice infected with the Δssa1 strain displayed substantial reductions in lung fungal burden during the innate phase (days 3 and 7) of the host response, whereas less pronounced reductions were observed during the adaptive phase (day 14) and mouse survival increased only by 5 d. Surprisingly, laccase activity assays revealed that Δssa1 was not laccase deficient, demonstrating that H99 does not require Ssa1 for laccase expression, which explains the CNS tropism we still observed in the Ssa1-deficient strain. Lastly, our immunophenotyping studies showed that Ssa1 directly promotes early M2 skewing of lung mononuclear phagocytes during the innate phase, but not the adaptive phase, of the immune response. We conclude that Ssa1's virulence mechanism in H99 is distinct and laccase-independent. Ssa1 directly interferes with early macrophage polarization, limiting innate control of C. neoformans, but ultimately has no effect on cryptococcal control by adaptive immunity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.