12 documents found, page 1 of 2
Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation
Rodrigues, Fernando José dos Santos; Cunha, Cristina; Aversa, Franco; Lacerda, João F.; Busca, Alessandro; Kunzai, Oliver; Grube, MatthiasBACKGROUND: The soluble pattern-recognition receptor known as long pentraxin 3 (PTX3) has a nonredundant role in antifungal immunity. The contribution of single-nucleotide polymorphisms (SNPs) in PTX3 to the development of invasive aspergillosis is unknown. METHODS: We screened an initial cohort of 268 patients undergoing hematopoietic stem-cell transplantation (HSCT) and their donors for PTX3 SNPs modifying th...
Neutrophil responses to Aspergillosis : new roles for old players
Cunha, Cristina; Kurzai, Oliver; Löffler, Jürgen; Aversa, Franco; Romani, Luigina; Carvalho, AgostinhoNeutrophils are professional phagocytic cells that play a crucial role in innate immunity. Through an assortment of antifungal effector mechanisms, neutrophils are essential in controlling the early stages of fungal infection. These mechanisms range from the production of reactive oxygen intermediates and release of antimicrobial enzymes to the formation of complex extracellular traps that aid in the eliminatio...
Host defense pathways against fungi : the basis for vaccines and immunotherapy
Carvalho, Agostinho; Cunha, Cristina; Iannitti, Andrea; Casagrande, Andrea; Bistoni, Francesco; Aversa, Franco; Romani, LuiginaFungal vaccines have long been a goal in the fields of immunology and microbiology to counter the high mortality and morbidity rates owing to fungal diseases, particularly in immunocompromised patients. However, the design of effective vaccination formulations for durable protection to the different fungi has lagged behind due to the important differences among fungi and their biology and our limited understand...
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of...
Carvalho, Agostinho; Cunha, Cristina; Almeida, A. J.; Osório, Nuno S.; Saraiva, Margarida; Coelho, Maria Teixeira; Pedreiro, Susana; Torrado, EgídioNon-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is b...
Immunity and tolerance to fungi in hematopoietic transplantation : principles a...
Carvalho, Agostinho; Cunha, Cristina; Bozza, Silvia; Moretti, Silvia; Massi-Benedetti, Cristina; Bistoni, Francesco; Aversa, Franco; Romani, LuiginaResistance and tolerance are two complementary host defense mechanisms that increase fitness in response to low-virulence fungi. Resistance is meant to reduce pathogen burden during infection through innate and adaptive immune mechanisms, whereas tolerance mitigates the substantial cost of resistance to host fitness through a multitude of anti-inflammatory mechanisms, including immunological tolerance. In exper...
TLR3 essentially promotes protective class I–restricted memory CD8+ T-cell resp...
Carvalho, Agostinho; De Luca, Antonella; Bozza, Silvia; Cunha, Cristina; D’Angelo, Carmen; Moretti, Silvia; Perruccio, Katia; Iannitti, Rossana G.Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8+ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8+ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain elusive. In the present study, we report that both CD4+ and CD8+...
Immunogenetic profiling to predict risk of invasive fungal diseases : where are...
Cunha, Cristina; Aversa, Franco; Bistoni, Giovanni; Casagrande, Andrea; Rodrigues, Fernando José dos Santos; Romani, Luigina; Carvalho, AgostinhoInvasive fungal diseases remain nowadays life-threatening conditions affecting multiple clinical settings. The onset of these diseases is dependent on numerous factors, of which the "immunocompromised" phenotype of the patients is the more often acknowledged. However, and despite comparable immune dysfunction, not all patients are ultimately susceptible to disease, suggesting that additional risk factors, likel...
The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 an...
Carvalho, Agostinho; Osório, Nuno S.; Saraiva, Margarida; Cunha, Cristina; Almeida, A. J.; Coelho, Maria Teixeira; Ludovico, Paula; Pedrosa, JorgeIn humans, allelic variants in Toll-like receptors (TLRs) associate with several pathologies. However, the underlying cellular and molecular mechanisms of this association remain largely unknown. Analysis of the human TLR9 promoter revealed that the C allele of the rs5743836 polymorphism generates several regulatory sites, including an IL-6-responding element. Here, we show that, in mononuclear cells carrying t...
Genetic susceptibility to aspergillosis in allogeneic stem-cell transplantation
Cunha, Cristina; Rodrigues, Fernando José dos Santos; Zelante, Teresa; Aversa, Franco; Romani, Luigina; Carvalho, AgostinhoInvasive aspergillosis (IA) is a major threat to positive outcomes for allogeneic stem-cell transplantation (allo-SCT) patients. Despite presenting similar degrees of immunosuppression, not all individuals at-risk ultimately develop infection. Therefore, the traditional view of neutropenia as a key risk factor for aspergillosis needs to be accommodated within new conceptual advances on host immunity and its rel...
Genetically-determined hyperfunction of the S100B/RAGE axis is a risk factor fo...
Cunha, Cristina; Giovannini, Gloria; Pierini, Antonio; Bell, Alain S.; Sorci, Guglielmo; Riuzzi, Francesca; Donato, RosarioInvasive aspergillosis (IA) is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT), although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE) axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE a...