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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...
Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal ca...
Carvalho, Agostinho; Giovannini, Gloria; De Luca, Antonella; D’Angelo, Carmen; Casagrande, Andrea; Iannitti, Rossana G.; Ricci, GiovanniWe thank Dr. Cristina Massi Benedetti for digital art and editing ; Recognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastroin...
Immunotherapy of aspergillosis
Carvalho, Agostinho; Cunha, Cristina; Bistoni, Francesco; Romani, LuiginaWe thank C. M. Benedetti for digital art and editing. ; Management of invasive aspergillosis in high-risk patients remains challenging. There is an increasing demand for novel therapeutic strategies aimed at enhancing or restoring antifungal immunity in immunocompromised patients. In this regard, modulation of specific innate immune functions and vaccination are promising immunotherapeutic strategies. Recent f...
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,...
DAMP signaling in fungal infections and diseases
Cunha, Cristina; Carvalho, Agostinho; Esposito, Antonella; Bistoni, Francesco; Romani, LuiginaFungal infections and diseases predominantly affect patients with deregulated immunity. Compelling experimental and clinical evidence indicate that severe fungal diseases belong to the spectrum of fungus-related inflammatory diseases. Some degree of inflammation is required for protection during the transitional response occurring temporally between the rapid innate and slower adaptive response. However, progre...
CD4+ T cell vaccination overcomes defective cross-presentation of fungal antige...
Luca, Antonella De; Iannitti, Rossana G.; Bozza, Silvia; Beau, Remi; Casagrande, Andrea; D’Angelo, Carmen; Moretti, Silvia; Cunha, CristinaAspergillus fumigatus is a model fungal pathogen and a common cause of infection in individuals with the primary immunodeficiency chronic granulomatous disease (CGD). Although primarily considered a deficiency of innate immunity, CGD is also linked to dysfunctional T cell reactivity. Both CD4+ and CD8+ T cells mediate vaccine-induced protection from experimental aspergillosis, but the molecular mechanisms leadi...
Immunity and tolerance to infections in experimental hematopoietic transplantation
Carvalho, Agostinho; Cunha, Cristina; Romani, LuiginaResistance and tolerance are two types of host defense mechanisms that increase fitness in response to fungi. Several genetic polymorphisms in pattern recognition receptors, most remarkably Toll-like receptors (TLRs), have been described to influence resistance and tolerance to aspergillosis in distinct clinical settings. TLRs on dendritic cells pivotally contribute in determining the balance between immunopath...
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...
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