Mutation of the WI-1 gene yields an attenuated Blastomyces dermatitidis strain that induces host resistance

Wüthrich, Marcel; Filutowicz, Hanna I.; Klein, Bruce S.

doi:10.1172/jci11037

Cited by 89 publications

(105 citation statements)

References 31 publications

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“…Therefore, a genetically engineered BAD1 null mutant was used as a vaccine. Live yeast of the null mutant injected subcutaneously protected mice against a lethal challenge with evidence of sterilizing immunity [27]. Vaccination in IFN-c or TNFa knock-out mice was still effective requiring either the reciprocal cytokine or GM-CSF.…”

Section: Attempts At Devising Vaccines Against Fungal Diseasesmentioning

confidence: 99%

Attempts at a peptide vaccine against paracoccidioidomycosis, adjuvant to chemotherapy

et al. 2008

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Section: Attempts At Devising Vaccines Against Fungal Diseasesmentioning

confidence: 99%

Attempts at a peptide vaccine against paracoccidioidomycosis, adjuvant to chemotherapy

et al. 2008

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“…P rotective immunity to infections with endemic dimorphic fungi, including Blastomyces dermatitidis, requires cellmediated immunity (CMI) 3 (1-4) and can be mediated by both CD4 ϩ (4) and CD8 ϩ T cells (5). On vaccination against B. dermatitidis, CD4 ϩ T cells are chiefly responsible for mediating immunity in immune-competent mice, although CD8 ϩ T cells can compensate when CD4 ϩ T cells are absent during the induction or afferent phase of the immune response (5).…”

Section: Differential Requirements Of T Cell Subsets For Cd40 Costimumentioning

confidence: 99%

“…55 yeast at each of two sites, dorsally and at the base of the tail, unless otherwise stated. Mice were infected intratracheally with 2 ϫ 10 3 isogenic wild-type strain 26199 yeast as described (3). Infected mice were monitored for survival or analyzed 2 wk after infection for extent of lung infection, determined by plating of homogenized lung and enumeration of yeast CFU on brain heart infusion (Difco) agar.…”

Section: Vaccination and Experimental Infection With B Dermatitidismentioning

confidence: 99%

Differential Requirements of T Cell Subsets for CD40 Costimulation in Immunity to Blastomyces dermatitidis

Wüthrich

Fisette

Filutowicz

et al. 2006

The Journal of Immunology

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Cell-mediated immunity and production of type 1 cytokines are the main defenses against pathogenic fungi. Ligation of CD40 by CD40L on T cells is critical for the induction of these immune responses in vivo. We explored the role of CD40/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by immunizing CD40−/− and CD40L−/− mice and analyzing their resistance to reinfection in a murine pulmonary model. In the absence of CD40 or CD40L, CD4+ cells failed to get primed or produce type 1 cytokine and impaired the generation of CD8+ T1 cells. The CD8+ T cell defect was not due to regulatory T cells or impaired APC maturation or Ag presentation to T cells. If CD4+ cells were first eliminated, vaccination of CD40−/− and CD40L−/− mice restored priming of CD8+ cells, type 1 cytokine production, and resistance. Hence, CD4+ and CD8+ cells differ sharply in their requirement for CD40/CD40L interaction during the generation of antifungal immunity. Despite the plasticity of T cell subsets in vaccine immunity, in absence of CD40/CD40L interaction, CD4+ cells may impede the priming of CD8+ cells at the cost of host survival against a lethal infectious disease.

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“…Implications for Vaccine Development in Immune-Deficient Hosts P rotective immunity to infections with dimorphic fungi such as Blastomyces dermatitidis requires type 1 (T1) 3 dependent cell-mediated immunity (1)(2)(3)(4) and can be mediated by CD4 ϩ (4) and CD8 ϩ T cells (5). Resistance by both T cell subsets requires production of T1 cytokines, particularly IFN-␥ and TNF-␣.…”

Section: Il-12 Is Required For Induction But Not Maintenance Of Protementioning

confidence: 99%

“…with 2 ϫ 10 2 to 2 ϫ 10 3 wildtype strain 26199 yeast as described previously (3). Infected mice were monitored for survival or analyzed 2 wk after infection for extent of lung infection, determined by plating of homogenized lung and enumeration of yeast colony-forming units on Brain heart infusion (Difco) agar.…”

Section: Vaccination In Vivo Treatment With Ril-12 and Experimentalmentioning

confidence: 99%

IL-12 Is Required for Induction but Not Maintenance of Protective, Memory Responses to Blastomyces dermatitidis: Implications for Vaccine Development in Immune-Deficient Hosts

Wüthrich

Warner²,

Klein

2005

The Journal of Immunology

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Cellular immunity mediated by T lymphocytes, in particular CD4+ and CD8+ type 1 (T1) cells, is the main defense against pathogenic fungi. IL-12 initiates T1 cell development and cell-mediated immunity, but it is unclear whether IL-12 contributes to the maintenance of an antifungal T1 response. In this study, we addressed the role of IL-12 for vaccine-induced memory T cell development against experimental pulmonary blastomycosis. CD4+ T cells absolutely required IL-12 to control a live genetically engineered attenuated strain of Blastomyces dermatitidis given s.c. as a vaccine, whereas CD8+ T cells were significantly less dependent on IL-12. Despite differential dependency of T cell subsets on IL-12 during vaccination, neither subset acquired memory immunity in the absence of IL-12. In contrast, adoptive transfer of immune CD4 T cells from wild-type mice into IL-12−/− mice showed that CD4+ T1 memory cells sustained a T1 cytokine profile and remained protective over a period of 6 mo posttransfer. Similarly, memory CD8 cells elicited in IL-12−/− mice with killed yeast and transient rIL-12 treatment (during vaccination) remained durable and protective after animals were rested for 3 mo. In conclusion, these studies demonstrate that once CD4 and CD8 cells have acquired a protective T1 phenotype they no longer require the presence of IL-12 to maintain antifungal protective memory.

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Mutation of the WI-1 gene yields an attenuated Blastomyces dermatitidis strain that induces host resistance

Cited by 89 publications

References 31 publications

Attempts at a peptide vaccine against paracoccidioidomycosis, adjuvant to chemotherapy

Attempts at a peptide vaccine against paracoccidioidomycosis, adjuvant to chemotherapy

Differential Requirements of T Cell Subsets for CD40 Costimulation in Immunity to Blastomyces dermatitidis

IL-12 Is Required for Induction but Not Maintenance of Protective, Memory Responses to Blastomyces dermatitidis: Implications for Vaccine Development in Immune-Deficient Hosts

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