The Cryptococcus neoformans GeneDHA1 Encodes an Antigen That Elicits a Delayed-Type Hypersensitivity Reaction in Immune Mice

Mandel, M. Alejandra; Grace, Greg G.; Orsborn, Kris I.; Schafer, Fredda; Murphy, Juneann W.; Orbach, Marc J.; Galgiani, John N.

doi:10.1128/.68.11.6196-6201.2000

Cited by 3 publications

(5 citation statements)

References 14 publications

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“…Using this information, we were able to identify in the cDNA library clones containing 12 different entire ORFs. Six of these genes turned out to be identical to previously described ones (Hamilton & Holdom, 1997;Mandel et al, 2000;Levitz et al, 2001;Biondo et al, 2002;Huang et al, 2002;Lian et al, 2005; Table 2).…”

Section: Fractionation and N-terminal Sequencingsupporting

confidence: 61%

“…In conclusion, we have identified 12 proteins that appear to be major components of cryptococcal supernatants. Some of these proteins have been previously characterized (Hamilton & Holdom, 1997;Levitz et al, 2001;Mandel et al, 2000;Biondo et al, 2002;Huang et al, 2002;Lian et al, 2005). We have described here three novel proteins, including peak-2 98 and 70 kDa MP, which both bear a prominent serine/threonine-rich region and a putative GPI anchor site.…”

Section: Newly Identified Genesmentioning

confidence: 89%

“…Accordingly, one non-MP antigen named d25 was shown to induce cell-mediated protection in experimentally infected mice (Biondo et al, 2002(Biondo et al, , 2003. Moreover, one other antigen capable of producing delayed-type hypersensitivity reactions has been described (Mandel et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Identification of major proteins secreted byCryptococcus neoformans

Biondo

Mancuso

Midiri

et al. 2006

FEMS Yeast Research

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The characterization of proteins secreted by Cryptococcus neoformans is of relevance to the identification of vaccine candidates, because concentrated supernatants from the fungus have been shown to be immunoprotective in previous studies. After fractionation of supernatants by anion exchange chromatography and preparative electrophoresis, we obtained the N-terminal amino acid sequences of 13 major proteins. Using a C. neoformans nucleotide database, we were able to clone and sequence the ORFs coding for 12 of these proteins. Some of the genes are identical to previously described ones, while six encode novel proteins, including four putative mannoproteins. The molecular characterization of these and other secreted products may provide useful information in the development of immune-based strategies to control cryptococcosis.

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Section: Fractionation and N-terminal Sequencingsupporting

confidence: 61%

Section: Newly Identified Genesmentioning

confidence: 89%

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Identification of major proteins secreted byCryptococcus neoformans

Biondo

Mancuso

Midiri

et al. 2006

FEMS Yeast Research

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“…Creative experiments over the last decade have shown that humoral immunity can play an important role in the elimination of cryptococci from the body [94,95]. With the use of molecular biology, several genes and encoded proteins have now been identified which may help elicit a protective immune response [96,[96][97][98]. In fact, with the use of molecular tools, it has now been possible to create C. neoformans strains which secrete host cytokines [99] which might aid in their own destruction.…”

Section: Immunologymentioning

confidence: 99%

Cryptococcus neoformans: A sugar-coated killer with designer genes

Perfect

2005

FEMS Immunology &Amp; Medical Microbiology

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Cryptococcus neoformans has become a common central nervous system pathogen as the immunocompromised populations enlarge world-wide. This encapsulated yeast has significant advantages for the study of fungal pathogenesis and these include: (1) a clinically important human pathogen; (2) a tractable genetic system; (3) advanced molecular biology foundation; (4) understanding of several virulence phenotypes; (5) well-studied pathophysiology; and (6) robust animal models. With the use of a sequenced genome and site-directed mutagenesis to produce specific null mutants, the virulence composite of C. neoformans has begun to be identified one gene at a time. Studies into capsule production, melanin synthesis, high temperature growth, metabolic pathways and a variety of signaling pathways have led to understandings of what makes this yeast a pathogen at the molecular level. Multiple principles of molecular pathogenesis have been demonstrated in virulence studies with C. neoformans. These include evolutionary differences between the varieties of C. neoformans in their genes for virulence, quantitative impact of genes on the virulence composite, species and site-specific importance of a virulence gene, gene expression correlation with its functional importance or phenotype and the impact of a pathogenesis gene on the host immune response. C. neoformans has now become a primary model to study molecular fungal pathogenesis with the goal of identifying drug targets or vaccine strategies.

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“…In summary, MPs, located in the C. neoformans envelope, are highly immunogenic and elicit DTH responses along with a partially protective immune response in mice (63,71,73). T-cell involvement and increased secretion of IFN-γ, TNF-a, IL-2 (75) and IL-12 (70) have been associated with particular mannoproteic determinants: MP98, MP88, MP84 and MP115 (65,66,67).…”

Section: Mannoproteinsmentioning

confidence: 99%

Protective Immunity Against Cryptococcus Neoformans Infection

Schop

2020

MJM

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Cryptococcus neoformans, the etiological agent of cryptococcosis, is an occasional opportunistic fungal pathogen of immune competent individuals. However, it is a relatively frequent cause of life-threatening meningoencephalitis and pulmonary infections in immunosuppressed hosts and is a leading mycological cause of morbidity and mortality among patients with AIDS in most parts of the world. The lack of an effective fungicidal regimen and the development of antifungal resistant strains suggest that continued investigation is necessary to devise immunotherapeutic strategies, drug targets and/or vaccines to combat C. neoformans infections. Until recently, cryptococcal virulence factors such as its polysaccharide capsule, macrophage parasitism, and its ability to induce an ineffective antibody mediated immune (AMI) response along with a non-protective type II (Th2) cell-mediated immune response have thwarted efforts to induce complete protective immunity against a lethal cryptococcal strain in murine models. The presence of C. neoformans antibodies in adult human serum suggests that immune competent individuals have difficulty resolving an early cryptococcal infection allowing for the establishment of a subclinical chronic infection. Recent studies have shown that pro-inflammatory cytokines, specifically interferon-g (IFN-g), associated with type I (Th1) cell-mediated immunity can successfully drive cell-mediated immune (CMI) responses to produce protective immunity to a second experimental C. neoformans infection in mice. This review will evaluate the intricacies of the host-cryptococcal interaction and discuss recent developments in C.neoformans research and the potential for human vaccines and/or drug therapies.

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The Cryptococcus neoformans GeneDHA1 Encodes an Antigen That Elicits a Delayed-Type Hypersensitivity Reaction in Immune Mice

Cited by 3 publications

References 14 publications

Identification of major proteins secreted byCryptococcus neoformans

Identification of major proteins secreted byCryptococcus neoformans

Cryptococcus neoformans: A sugar-coated killer with designer genes

Protective Immunity Against Cryptococcus Neoformans Infection

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