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Papers by Roberta Spaccapelo

PLOS Pathogens, Nov 16, 2016

Expression of proteins encoding blood-stage exported proteins in blood- and liver-stages... more Expression of proteins encoding blood-stage exported proteins in blood- and liver-stages</p

PLOS Pathogens, Nov 16, 2016

Features of tagged members of the pir, fam-a and &... more Features of tagged members of the pir, fam-a and fam-b multigene families</p

PLOS Pathogens, Nov 16, 2016

These mutants contain the following pairs of genes tagged with either mCherry or GFP: &l... more These mutants contain the following pairs of genes tagged with either mCherry or GFP: fam-a1/fam-a2 (2 independent mutants; panel A, B), fam-b1/fam-b2 (panel C) and pir1/pir3 (panel D); RMgm ID as indicated in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005917#ppat.1005917.t002" target="_blank">Table 2</a>. Localisation of mCherry-tagged members in the trophozoite stage (upper two rows) and in the schizont (low row) stage. Parasite nuclei are stained with Hoechst, BF bright field. scale bar: 5μm.</p

Frontiers in Microbiology, Jun 16, 2023

PLOS ONE, Oct 24, 2014

Molecular structure of TLR agonists GLA, R848, and CS/D-3M051 conjugate.</p

bioRxiv (Cold Spring Harbor Laboratory), Jul 12, 2021

The Journal of Immunology

Resistance and susceptibility of mice to systemic infection with the fungus Candida albicans are ... more Resistance and susceptibility of mice to systemic infection with the fungus Candida albicans are associated with the preferential expansion of Th1 and Th2 cells, respectively. In this study, endogenous production of TGF-beta was found to be increased soon after infection of healer mice with a live vaccine strain of the fungus, but down-regulated in nonhealer mice with virulent yeast challenge. Although not affecting the outcome of primary challenge, serologic ablation of TGF-beta in the former animals abrogated development of acquired resistance and resulted in impaired production of IL-12/IFN-gamma and higher expression of IL-4/IL-10 at the time of reinfection with virulent yeast. A CD4+ population expressing the memory phenotype, CD44highMEL-14low, which appeared to be expanded by yeast infection of nonhealer mice, was similarly increased in the healer mice by anti-TGF-beta treatment. In vitro rTGF-beta impaired the candidacidal function of IFN-gamma-activated macrophages. Yet in ...

The Journal of Immunology

In murine models of systemic candidiasis, healing and nonhealing patterns of disease are associat... more In murine models of systemic candidiasis, healing and nonhealing patterns of disease are associated with preferential expansion of Th1 and Th2 cells, respectively. As previous studies have shown IL-12 to be expressed transcriptionally in healer mice and to be required for Th1 development in vitro, this cytokine might play a role in Candida-driven Th1 cell differentiation in vivo. In the present study, IL-12-neutralizing Abs or recombinant IL-12 were administered to mice with healing or progressive candidiasis, respectively, and the animals were monitored for mortality, resistance to reinfection, serum levels of specific Abs, and IFN-gamma, IL-4, and IL-10 message/protein expression by CD4+ cells. In self-limiting infection by a yeast vaccine strain, neutralization of IL-12 ablated development of acquired anticandidal resistance and led to appearance of Candida-specific IgE and IL-4-producing cells. In mice with progressive systemic disease as well as in a mucosal infection model, ad...

The Journal of Immunology

Previous work has shown that in hybrid (BALB/cCr x DBA/2Cr)F1 mice the development of a fatal dis... more Previous work has shown that in hybrid (BALB/cCr x DBA/2Cr)F1 mice the development of a fatal disseminated disease by systemic infection with virulent Candida albicans is associated with the detection of strong Th2-like responses. However, a predominant Th1-like response and long-lived antifungal protection are induced by vaccinating these mice with live blastospores of attenuated C. albicans strains. When injected into DBA/2Cr mice, one such live vaccine strain was found in the present study to result in a progressive disease characterized by strong Th2 responses. Elevated serum IgG1, IgA, and IgE responses, weak or absent footpad reactions, sustained production in vitro of Th2 (IL-4 and IL-10) but not Th1 (IL-2 and IFN-gamma) cytokines by CD4+ cells, and eosinophilia were all detected in DBA/2 mice after infection with the attenuated vaccine. This was in marked contrast with the development of strong Th1 responses and persistent anticandidal protection in similarly infected, H-2-c...

The Journal of Immunology

To investigate the role and effect of IL-2 in the genesis of Th1 and Th2 responses to Candida alb... more To investigate the role and effect of IL-2 in the genesis of Th1 and Th2 responses to Candida albicans in vivo, we assessed the levels of IL-2 production and the Ag-specific proliferative response in mice with healing or nonhealing infection and the effects of IL-2 neutralization or administration on the course and outcome of infection and on the type of CD4+ Th immunity elicited. High levels of IL-2 production and Ag-specific proliferation in vitro correlated with disease progression in susceptible mice. In contrast, resolution of infection in resistant mice was accompanied by the induction of Ag-specific hyporesponsiveness and impaired IL-2 production. Progression of infection did not occur in susceptible mice treated with anti-IL-2 or anti-IL-2R mAbs; conversely, disease resolution was prevented in resistant mice treated with IL-2. CD4+ Th1 cell responses were present in BALB/c mice rendered resistant by IL-2 neutralization and CD4+ Th2 responses in mice rendered susceptible by I...

Journal of Infection and Public Health

PLOS Pathogens, 2016

A. Features of transcription of pir, fam-... more A. Features of transcription of pir, fam-a and fam-b genes in the two P. berghei reference lines (line 1 and line 2) based on RNAseq data (from[<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005917#ppat.1005917.ref033" target="_blank">33</a>] and shown in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005917#ppat.1005917.s007" target="_blank">S1 Table</a>). Transcribed genes are genes with an FPKM value above the cut-off level of 21. Total transcript abundance is the sum of all FPKM values observed in the different blood stages (see B). The fold up-down regulation is based on the difference in FPKM values of individual genes between blood stages of the two different parasite lines (see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005917#ppat.1005917.s001" target="_blank">S1 Fig</a>). B. Percentage of genes transcribed in the different blood stages (see A). Ring, red; trophozoite, green; schizont, purple; gametocyte, black. C. Total transcript abundance in the different blood stages: mean and standard deviation of total transcript abundance of all FPKM values observed in the different blood stages (see A). D. Percentage of non-transcribed genes (light grey) and genes with less (grey) or more (black) than 1.5x difference in transcript abundance between blood stages of two different parasite lines (see A). The coloured circles show the genes with >1.5 fold down-or upregulation in the four different blood stages (see B).</p

PLOS Pathogens, 2016

The tree was estimated using RAxML and a GTR+Γ model. Branches subtended by nodes with &... more The tree was estimated using RAxML and a GTR+Γ model. Branches subtended by nodes with >75 bootstrap support are shown in bold. Robust basal nodes are indicated by black squares with bootstrap proportions (above node) and Bayesian posterior probabilities (beneath node). At right, coloured blocks indicate the species to which a terminal node belongs. Clades of orthologs that display positional conservation are indicated with green blocks; where a sequence has been lost secondarily in a species is shown by an ‘X’. The tree is rooted using an out-group comprising single copy fam-a orthologs from primate Plasmodium species. The phylogeny is subdivided into four sections: genes located at the conserved, ‘ancestral’ locus on chromosome 13 (below line i); genes found at loci conserved across RMP species (between lines i and ii); and a robust clade of species-specific paralogs derived from a conserved locus on chromosome 6 or 13 (between lines ii and iii); a robust clade of species-specific paralogs derived from a conserved locus on chromosome 8 (above line iii).Transcription levels (shown as different coloured and sized circles) in blood stages are shown for individual genes based on RNAseq data (FPKM values) (from [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005917#ppat.1005917.ref033" target="_blank">33</a>] and <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005917#ppat.1005917.s007" target="_blank">S1 Table</a>). Expression levels as shown by four different sized circles: Class 1 (smallest circle): 2-8x the threshold level; class 2: 8-16x the threshold; class 3 (largest circle): >16x the threshold.</p

PLOS Pathogens, 2016

A. Fluorescence-microscopy analysis of members of the fam-a&... more A. Fluorescence-microscopy analysis of members of the fam-a, fam-b and pir multigene family in live liver-stages. The parasites expressing mCherry-tagged Fam-b2 and PIR1 also express cytoplasmic GFP (cyt GFP; green). B. IFA-analysis of fixed liver-stages using anti-mCherry (red) anti-PbEXP1 (green) antibodies. PbEXP1 is a parasitophorous vacuole membrane resident protein. C Fluorescence-microscopy analysis of expression of SMAC and IBIS, exported proteins encoded by single-copy genes in live liver-stages. Nuclei are stained with Hoechst-33342 (blue); scale bar: 10μm.</p

PLOS Pathogens, Nov 16, 2016

Expression of proteins encoding blood-stage exported proteins in blood- and liver-stages... more Expression of proteins encoding blood-stage exported proteins in blood- and liver-stages</p

PLOS Pathogens, Nov 16, 2016

Features of tagged members of the pir, fam-a and &... more Features of tagged members of the pir, fam-a and fam-b multigene families</p

PLOS Pathogens, Nov 16, 2016

Frontiers in Microbiology, Jun 16, 2023

PLOS ONE, Oct 24, 2014

Molecular structure of TLR agonists GLA, R848, and CS/D-3M051 conjugate.</p

bioRxiv (Cold Spring Harbor Laboratory), Jul 12, 2021

The Journal of Immunology

Journal of Infection and Public Health

PLOS Pathogens, 2016