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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...
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...
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, EgídioWe are grateful to Paulo Vieira, Cecília Leão, Manuel T. Silva, Nuno Sousa, Jorge Correia- Pinto, Joana Palha, Margarida Correia-Neves, Margarida Lima and Matthew Berry for all their input throughout these studies and critical reading of the manuscript. We are grateful to the patients who joint this study as well as to all members of the Life and Health Sciences Research Institute and School of Health Sciences,...
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...
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...
Non-hematopoietic cells contribute to protective tolerance to Aspergillus fumig...
Luca, Antonella De; Bozza, Silvia; Zelante, Teresa; Zagarella, Silvia; Angelo, Carmen de; Perruccio, Katia; Vacca, Carmine; Carvalho, AgostinhoInnate responses combine with adaptive immunity to generate the most effective form of anti-Aspergillus immune resistance. Whereas the pivotal role of dendritic cells in determining the balance between immunopathology and protective immunity to the fungus is well established, we determined that epithelial cells (ECs) also contributes to this balance. Mechanistically, EC-mediated protection occurred through a To...
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