A5037274141- Bacterial Infections and Vaccines
- Bacillus and Francisella bacterial research
- Pneumonia and Respiratory Infections
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Antimicrobial Resistance in Staphylococcus
- Inflammatory mediators and NSAID effects
- Poxvirus research and outbreaks
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Bacterial Genetics and Biotechnology
- NF-κB Signaling Pathways
- Peripheral Neuropathies and Disorders
- Renal and related cancers
- Inhalation and Respiratory Drug Delivery
- Immunodeficiency and Autoimmune Disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Microbial infections and disease research
- Streptococcal Infections and Treatments
- Inflammasome and immune disorders
- T-cell and B-cell Immunology
- Peptidase Inhibition and Analysis
- Blood disorders and treatments
- Influenza Virus Research Studies
- Signaling Pathways in Disease
Toscana Life Sciences
2011-2024
GlaxoSmithKline (Italy)
2024
GlaxoSmithKline (India)
2021
Novartis (Italy)
2011-2015
Novartis (Switzerland)
2015
Newron Pharmaceuticals (Italy)
2013
University of Siena
2003-2012
University of Florence
2004-2005
The University of Sydney
2005
Pfizer (Italy)
2004
Helicobacter pylori toxin, VacA, damages the gastric epithelium by erosion and loosening of tight junctions. Here we report that VacA also interferes with T cell activation two different mechanisms. Formation anion-specific channels prevents calcium influx from extracellular milieu. The transcription factor NF-AT thus fails to translocate nucleus activate key cytokine genes. A second, channel-independent mechanism involves intracellular signaling through mitogen-activated protein kinases...
Anthrax is an infection caused by pathogenic strains of Bacillus anthracis, which secretes a three-component toxic complex consisting protective antigen (PA), edema factor (EF), and lethal (LF). PA forms binary complexes with either LF or EF mediates their entry into host cells. Although the initial phases bacterial growth occur in lymph node, fails to mount effective immune response. Here, we show that LT ET are potent suppressors human T cell activation proliferation triggered through...
Abstract Objective Human Lyme arthritis caused by Borrelia burgdorferi is characterized an inflammatory infiltrate that consists mainly of neutrophils and T cells. This study was undertaken to evaluate the role innate acquired immune responses elicited neutrophil‐activating protein A (NapA) B in patients with arthritis. Methods Serum anti‐NapA antibodies were measured 27 30 healthy control subjects. The cytokine profile synovial fluid cells specific for NapA investigated 5 induced monocytes...
Abstract Induction of persistent protective immune responses is a key attribute successful vaccine formulation. MF59 adjuvant, an oil-in-water emulsion used in human vaccines, known to induce high-affinity functional Ab titers and memory B cells, but how it really shapes the Ag-specific cell compartment poorly documented. In this study, we characterized Ab- wild-type mice immunized with HlaH35L, Staphylococcus aureus Ag measurable responses, formulated or aluminum salts, focusing on germinal...
SslE is a zinc-metalloprotease involved in the degradation of mucin substrates and recently proposed as potential vaccine candidate against pathogenic E. coli. In this paper, by exploiting human vitro model mucus-secreting cells, we demonstrated that bacteria expressing have metabolic benefit which results an increased growth rate postulating importance antigen enhancing coli fitness. We also observed expression facilitates penetration mucus favouring adhesion to host cells. Moreover, found...
Following ligand binding the TCR segregates to plasma membrane microdomains, termed lipid rafts, characterized by a highly ordered structure favoring partitioning of glycosyl phosphatidyl inositol-linked costimulatory receptors and acylated signaling molecules. Here we show that inducible association key proteins with rafts is dependent on actin cytoskeleton through mechanism involving raft coalescence. Although are required for full activation TCR-dependent tyrosine phosphorylation cascade...
In addition to antagonizing inflammation by inhibiting the activity of cyclooxygenases (COX), nonsteroidal anti-inflammatory drugs (NSAID) block T-cell activation. The immunosuppressant NSAID correlates with their ability transcription factors required for expression inducible response genes triggered antigen receptor (TCR) engagement. Whereas inhibition nuclear factor-κB aspirin and sodium salicylate can be partly accounted binding IκB kinase-β, broad range transcriptional targets suggests...
Pathogenic strains of Bacillus anthracis produce two potent toxins, lethal toxin (LT), a metalloprotease that cleaves mitogen-activated protein kinase kinases, and oedema (ET), calcium/calmodulin-dependent adenylate cyclase. Emerging evidence indicates role for both toxins in suppressing the initiation innate adaptive immune responses, which are essential to keep infection under control. Here we show LT ET inhibit chemotaxis T-cells macrophages by subverting signalling CXC CC chemokine...
Recurrences develop in up to 20-50% of patients with acute pericarditis. Although different causes recurrent pericarditis have been identified, the etiology remains obscure most cases which are therefore labelled as idiopathic. Autoinflammatory syndromes include familial Mediterranean fever (FMF), due mutations MEFV gene, and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), TNFRSF1A gene. Recurrent is a common feature both conditions, but it rarely occurs alone....
Phospholipases are produced from bacterial pathogens causing very different diseases. One of the most intriguing aspects phospholipases is their potential to interfere with cellular signaling cascades and modulate host–immune response. Here, we investigated role innate acquired immune responses elicited by Chlamydophila pneumoniae phospholipase D (CpPLD) in pathogenesis atherosclerosis. We evaluated cytokine chemokine production induced CpPLD healthy donors’ monocytes vivo activated T cells...
Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein ubiquitously expressed by Neisseria meningitidis strains and an antigen of the Bexsero® vaccine. NHBA binds heparin through conserved Arg-rich region that target two proteases, meningococcal NalP human lactoferrin (hLf). In this work, in vitro studies showed recombinant protein was able to bind epithelial cells mutations tract abrogated binding. All N-terminal C-terminal fragments generated or hLf cleavage, regardless...
The adenylate cyclase toxin (CyaA) released by Bordetella pertussis is an essential virulence factor for colonization of the host. This inhibits migration and activation phagocytes, thereby preventing bacterial killing. In addition, CyaA interferes with initiation adaptive immunity misdirecting dendritic cell differentiation to a suppressive rather than stimulatory phenotype. Here we show that directly affects responses catalyzing cyclic AMP (cAMP) production in peripheral blood lymphocytes....
Abstract Background We determined the relationships between cytokine expression in sputum and clinical data to characterize understand chronic obstructive pulmonary disease (COPD) exacerbations people with COPD. Methods measured 30 cytokines 936 samples, collected at stable state exacerbation visits from 99 participants Acute Exacerbation Respiratory InfectionS COPD (AERIS) study (ClinicalTrials.gov NCT01360398). their longitudinal examined differential based on status or type. Results Of...
The adjuvanticity of bacterial adenylate cyclase toxins has been ascribed to their capacity, largely mediated by cAMP, modulate APC activation, resulting in the expression Th2-driving cytokines. On other hand, cAMP demonstrated induce a Th2 bias when present during T cell priming, suggesting that elevating may directly affect Th1/Th2 balance. Here we have investigated effects on human CD4(+) differentiation two toxins, Bacillus anthracis edema toxin (ET) and Bordetella pertussis CyaA, which...
The Bordetella pertussis adenylate cyclase toxin (CyaA) assists infection by potently suppressing the host immune response. Although CyaA effectively targets T lymphocytes, its putative receptor on these cells is unknown. Here, we show that binds to via β2 integrin LFA-1 in active conformation. clusters with at synapse (IS), from which it induces premature disengagement of concomitant dissipation talin, tethers underlying actin cytoskeleton. CyaA-induced redistribution was cAMP- and protein...
The nuclear factor of activated T-cells (NFAT) family transcription factors play a key role in the control cytokine gene expression T-cells. Although initially identified T-cells, recent data have unveiled unanticipated roles for NFATs development, proliferation, and differentiation other tissues. Here we report identification, cDNA cloning, functional characterization new isoform NFAT1 highly expressed mouse brain. This isoform, which named NFAT1-D, is identical to throughout N-terminal...
Although the contribution of carbohydrate catabolism to bacterial colonization and infection is well recognized, transcriptional changes during these processes are still unknown. In this study, we have performed comparative global gene expression analysis GBS in sugar-free versus high glucose milieu. The revealed a differential genes involved metabolism, transport host-pathogen interaction. Many them appeared be among previously reported controlled by CovRS two-component system. Indeed,...
In this study, we have characterized the functional properties of a novel Escherichia coli antigen named EsiB (E. secretory immunoglobulin A-binding protein), recently reported to protect mice from sepsis. Gene distribution analysis panel 267 strains representative different E. pathotypes revealed that esiB is preferentially associated with extraintestinal strains, while gene rarely found in either intestinal or nonpathogenic strains. These findings were supported by presence anti-EsiB...
Neisseria meningitidis is a human pathogen that can cause fatal sepsis and meningitis once it reaches the blood stream nervous system. Here we demonstrate fragment, released upon proteolysis of surface-exposed protein Neisserial Heparin Binding Antigen (NHBA), by bacterial protease NalP, alters endothelial permeability inducing internalization adherens junction VE-cadherin. We found C2 rapidly accumulates in mitochondria where induces production reactive oxygen species: latter are required...