The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Alberto Mantovani - One of the best experts on this subject based on the ideXlab platform.
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the long pentraxin ptx3 as a humoral innate immunity functional player and biomarker of infections and sepsis
Frontiers in Immunology, 2019Co-Authors: Remi Porte, Alberto Mantovani, Sadaf Davoudian, Fatemeh Asgari, Raffaella ParenteAbstract:The first line of defense in innate immunity is provided by cellular and humoral mediators. Pentraxins are a superfamily of phylogenetically conserved humoral mediators of innate immunity. PTX3, the first long pentraxin identified, is a soluble pattern recognition molecule rapidly produced by several cell types in response to primary pro-inflammatory signals and microbial recognition. PTX3 acts as an important mediator of innate immunity against pathogens of fungal, bacterial and viral origin, and as a regulator of inflammation, by modulating complement activation and cell extravasation, and facilitating pathogen recognition by myeloid cells. In sepsis, PTX3 plasma levels are associated with severity of the condition, patient survival, and response to therapy. In combination with other established biomarkers, PTX3 could improve stratification of sepsis patients and thus, complement the system of classification and monitoring of this disease.
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the long pentraxin ptx3 as a link between innate immunity tissue remodeling and cancer
Frontiers in Immunology, 2019Co-Authors: Matteo Stravalaci, Alberto Mantovani, Antonio Inforzato, Elena MagriniAbstract:The innate immune system comprises a cellular and a humoral arm. Humoral pattern recognition molecules include complement components, collectins, ficolins, and Pentraxins. These molecules are involved in innate immune responses by recognizing microbial moieties and damaged tissues, activating complement, exerting opsonic activity and facilitating phagocytosis, and regulating inflammation. The long pentraxin PTX3 is a prototypic humoral pattern recognition molecule that, in addition to providing defence against infectious agents, plays several functions in tissue repair and regulation of cancer-related inflammation. Characterization of the PTX3 molecular structure and biochemical properties, and insights into its interactome and multiple roles in tissue damage and remodelling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.
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the dual complexity of ptx3 in health and disease a balancing act
Trends in Molecular Medicine, 2016Co-Authors: Elena Magrini, Alberto Mantovani, Cecilia GarlandaAbstract:The humoral arm of innate immunity is complex and includes various molecules that serve as markers of inflammation with complementary characteristics, such as the short Pentraxins C-reactive protein (CRP) and serum amyloid P (SAP) and the long pentraxin PTX3. There is a growing amount of evidence - including mouse and human genetics - that suggests that PTX3 is essential in conferring host resistance against selected pathogens and, moreover, that it plays a dual antagonistic role in the regulation of inflammation. Dissection of such a yin-and-yang role of Pentraxins in immunity and inflammation is timely and significant as it may pave the way for better clinical exploitation against various diseases.
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the Pentraxins ptx3 and sap in innate immunity regulation of inflammation and tissue remodelling
Journal of Hepatology, 2016Co-Authors: Antonio Inforzato, Massimo Messa, Marialuisa Barbagallo, Elena Magrini, Alberto MantovaniAbstract:Summary Pentraxins are a superfamily of fluid phase pattern recognition molecules conserved in evolution and characterized by a cyclic multimeric structure. C-reactive protein (CRP) and serum amyloid P component (SAP) constitute the short pentraxin arm of the superfamily. CRP and SAP are produced in the liver in response to IL-6 and are acute phase reactants in humans and mice respectively. In addition SAP has been shown to affect tissue remodelling and fibrosis by stabilizing all types of amyloid fibrils and by regulating monocyte to fibrocyte differentiation. Pentraxin 3 (PTX3) is the prototype of the long pentraxin arm. Gene targeted mice and genetic and epigenetic studies in humans suggest that PTX3 plays essential non-redundant roles in innate immunity and inflammation as well as in tissue remodelling. Recent studies have revealed the role of PTX3 as extrinsic oncosuppressor, able to tune cancer-related inflammation. In addition, at acidic pH PTX3 can interact with provisional matrix components promoting inflammatory matrix remodelling. Thus acidification during tissue repair sets PTX3 in a tissue remodelling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.
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Pentraxins and collectins friend or foe during pathogen invasion
Trends in Microbiology, 2015Co-Authors: Patrick C Reading, Alberto Mantovani, Sébastien Jaillon, Suresh MahalingamAbstract:Innate immunity serves as the frontline defence against invading pathogens. Despite decades of research, new insights are constantly challenging our understanding of host-elicited immunity during microbial infections. Recently, two families of humoral innate immune proteins, Pentraxins and collectins, have become a major focus of research in the field of innate immunity. Pentraxins and collectins are key players in activating the humoral arm of innate immunity, taking centre stage in immunoregulation and disease modulation. However, increasing evidence suggests that Pentraxins and collectins can also mediate pathogenic effects during some infections. Herein, we discuss the protective and pathogenic effects of Pentraxins and collectins, as well as their therapeutic significance.
Giuseppe Peri - One of the best experts on this subject based on the ideXlab platform.
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pentraxin 3 in acute respiratory distress syndrome an early marker of severity
Critical Care Medicine, 2008Co-Authors: Tommaso Mauri, Giuseppe Peri, Alberto Mantovani, Andrea Coppadoro, Giacomo Bellani, M Bombino, Nicolò Patroniti, Antonio PesentiAbstract:Objective: Pentraxin 3 is a fluid phase receptor involved in innate immunity. It belongs to the Pentraxins family, as C-reactive protein does. Pentraxin 3 is produced by a variety of tissue cells, whereas only the liver produces C-reactive protein. Pentraxin 3 plays a unique role in the regulation of inflammation. Acute lung injury and acute respiratory distress syndrome are characterized by an important inflammatory reaction. We investigated the role of pentraxin 3 as a marker of severity and outcome predictor of acute lung injury and acute respiratory distress syndrome. Design: We measured circulating pentraxin 3 and C-reactive protein levels within 24 hrs from intubation (day 1), after 24 hrs from the first sample, then every 3 days for the first month and then once a week, until discharge from the intensive care unit. Pentraxin 3 was also measured in bronchoalveolar lavages, performed when clinically indicated. Setting: One university medical center general intensive care unit. Patients: The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria). Interventions: None. Measurements and Main Results: Pentraxin 3 plasma levels were high with a peak on the first day (median 71.05 ng/mL, interquartile range 52.37-117.38 ng/mL, normal values <2 ng/mL), declining thereafter. C-reactive protein peaked later and remained at relatively high values. Out of several day 1 parameters, pentraxin 3 was the only significant difference between survivors and nonsurvivors. Pentraxin 3 levels were positively correlated with lung injury score values (p < 0.001) and number of organ failures (p < 0.001). Pentraxin 3 was present in bronchoalveolar lavages fluids (5.03 ng/mL, interquartile range 1.52-8.48 ng/mL) and bronchoalveolar lavages positive to bacterial culture were associated with significantly higher pentraxin 3 values (p < 0.05). Conclusions: The results presented here show that pentraxin 3 is elevated in acute lung injury and acute respiratory distress syndrome and that its levels correlate with parameters of lung injury and systemic involvement. The clinical and pathophysio-logical significance of pentraxin 3 in acute lung injury and acute respiratory distress syndrome deserves further scrutiny.
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The long pentraxin PTX3 in vascular pathology.
Vascular Pharmacology, 2006Co-Authors: Alberto Mantovani, Giuseppe Peri, Yeny Martinez De La Torre, Roberto LatiniAbstract:Pentraxins are a family of evolutionarily conserved multifunctional pattern-recognition proteins characterized by a cyclic multimeric structure. Based on the primary structure of the subunit, the Pentraxins are divided into two groups: short Pentraxins and long Pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short Pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the liver in response to IL-6, while PTX3 is produced by a variety of tissues and cells and in particular by innate immunity cells in response to proinflammatory signals and Toll-like receptor (TLR) engagement. PTX3 interacts with several ligands, including growth factors, extracellular matrix components and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes, acting as a predecessor of antibodies. In addition, PTX3 is essential in female fertility by acting as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor acting as a non-redundant component of the humoral arm of innate immunity and involved in tuning inflammation, in matrix deposition and female fertility.
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the pattern recognition receptor ptx3 is recruited at the synapse between dying and dendritic cells and edits the cross presentation of self viral and tumor antigens
Blood, 2006Co-Authors: Paramita Baruah, Giuseppe Peri, Alberto Mantovani, Patrizia Roverequerini, Antonella Propato, Ingrid E Dumitriu, Vincenzo Russo, Raffaella Fontana, Daniele Accapezzato, Vincenzo BarnabaAbstract:Pentraxins are soluble pattern recognition receptors with a dual role: protection against extracellular microbes and autoimmunity. The mechanisms by which they accomplish these tasks are not yet fully understood. Here we show that the prototypic long pentraxin PTX3 is specifically recruited at both sides of the phagocytic synapse between dendritic cells (DCs) and dying cells and remains stably bound to the apoptotic membranes (estimated half-time > 36 hours). Apoptotic cells per se influence the production of PTX3 by maturing DCs. When both microbial stimuli and dying cells are present, PTX3 behaves as a flexible adaptor of DC function, regulating the maturation program and the secretion of soluble factors. Moreover a key event associated with autoimmunity (ie, the cross-presentation of epitopes expressed by apoptotic cells to T cells) abates in the presence of PTX3, as evaluated using self, viral, and tumor-associated model antigens (vinculin, NS3, and MelanA/MART1). In contrast, PTX3 did not influence the presentation of exogenous soluble antigens, an event required for immunity against extracellular pathogens. These data suggest that PTX3 acts as a third-party agent between microbial stimuli and dying cells, contributing to limit tissue damage under inflammatory conditions and the activation of autoreactive T cells.
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elevated plasma levels of the long pentraxin pentraxin 3 in severe dengue virus infections
Journal of Medical Virology, 2005Co-Authors: Albert T A Mairuhu, Giuseppe Peri, Tatty E Setiati, Erik C Hack, Penelopie Koraka, Augustinus Soemantri, Albert D M E Osterhaus, Dees P M Brandjes, Jos W M Van Der Meer, Alberto MantovaniAbstract:C-reactive protein is one of the most widely used indicators of the response of acute-phase proteins. The measurement of C-reactive protein in dengue, however, is clinically not useful, because of marginally elevated levels and absent association with disease severity. The prototypic long pentraxin, pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients. The potential involvement of pentraxin 3 in dengue and its aptitude to predict more severe disease or poor clinical outcome has not been studied previously. We therefore measured pentraxin 3 plasma levels in 44 dengue virus infected patients. Pentraxin 3 levels were strikingly higher when compared to C-reactive protein levels, with highest pentraxin 3 values observed in the first 7 days after the onset of symptoms. Median pentraxin 3 levels at admission and peak levels during follow up were higher in patients suffering from dengue shock syndrome (at admission: 119.3 ng/ml [interquartile range 61.8--188.7], peak values during follow up: 147.9 ng/ml [interquartile range 85.7--204.3]) compared to levels found in patients with dengue fever and dengue hemorrhagic fever (at admission: 59.0 ng/ml [interquartile range 28.6--100.3], P=0.040; peak values during follow up: 80.8 ng/ml [interquartile range 36.1--168.1], P=0.020). Our results indicate that pentraxin 3 seems to be a marker of infection better than C-reactive protein in dengue. The role of pentraxin 3 in the pathogenesis of dengue and its potential as an early prognostic indicator of disease severity needs further assessment.
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production of the soluble pattern recognition receptor ptx3 by myeloid but not plasmacytoid dendritic cells
European Journal of Immunology, 2003Co-Authors: Andrea Doni, Giuseppe Peri, Alberto Mantovani, Fabio Pasqualini, Luca Vago, Luigina Romani, Paola Allavena, Marcello ChieppaAbstract:PTX3 is a prototypic of long pentraxin consisting of an N-terminal portion coupled to a C-terminal pentraxin domain, the latter related to short Pentraxins (C-reactive protein and serum amyloid P component). PTX3 is a soluble pattern recognition receptor, which plays a non-redundant role in resistance against selected pathogens and in female fertility. The present study was designed to analyze the production of PTX3 by human dendritic cells (DC) and to define the role of different innate immunity receptors in its induction. Human monocyte-derived DC produced copious amounts of PTX3in response to microbial ligands engaging different members of the Toll-like receptor (TLR) family (TLR1 through TLR6), whereas engagement of the mannose receptor had no substantial effect. DC werebetter producers of PTX3 than monocytes and macrophages. Freshly isolated peripheral blood myeloid DC produced PTX3 in response to diverse microbial stimuli. In contrast, plasmacytoid DC exposed to influenza virus or to CpG oligodeoxynucleotides engaging TLR9, did not produce PTX3. PTX3-expressing DC were present in inflammatory lymph nodes from HIV-infected patients. These results suggest that DC of myelomonocytic origin are a major source of PTX3, a molecule which facilitates pathogen recognition and subsequent activation of innate and adaptive immunity.
Antonio Inforzato - One of the best experts on this subject based on the ideXlab platform.
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the complement system in aspergillus fumigatus infections and its crosstalk with Pentraxins
FEBS Letters, 2020Co-Authors: Raffaella Parente, Barbara Bottazzi, Andrea Doni, Cecilia Garlanda, Antonio InforzatoAbstract:Aspergillosis is a life-threatening infection mostly affecting immunocompromised individuals and primarily caused by the saprophytic fungus Aspergillus fumigatus. At the host-pathogen interface, both cellular and humoral components of the innate immune system are increasingly acknowledged as essential players in the recognition and disposal of this opportunistic mold. Fundamental hereof is the contribution of the complement system, which deploys all three activation pathways in the battle against A. fumigatus, and functionally cooperates with other soluble pattern recognition molecules, including Pentraxins. In particular, preclinical and clinical observations point to the long pentraxin PTX3 as a nonredundant and complement-dependent effector with protective functions against A. fumigatus. Based on past and current literature, here we discuss how the complement participates in the immune response to this fungal pathogen, and illustrate its crosstalk with the Pentraxins, with a focus on PTX3. Emphasis is placed on the molecular mechanisms underlying such processes, the genetic evidence from human epidemiology, and the translational potential of the currently available knowledge.
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the long pentraxin ptx3 as a link between innate immunity tissue remodeling and cancer
Frontiers in Immunology, 2019Co-Authors: Matteo Stravalaci, Alberto Mantovani, Antonio Inforzato, Elena MagriniAbstract:The innate immune system comprises a cellular and a humoral arm. Humoral pattern recognition molecules include complement components, collectins, ficolins, and Pentraxins. These molecules are involved in innate immune responses by recognizing microbial moieties and damaged tissues, activating complement, exerting opsonic activity and facilitating phagocytosis, and regulating inflammation. The long pentraxin PTX3 is a prototypic humoral pattern recognition molecule that, in addition to providing defence against infectious agents, plays several functions in tissue repair and regulation of cancer-related inflammation. Characterization of the PTX3 molecular structure and biochemical properties, and insights into its interactome and multiple roles in tissue damage and remodelling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.
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the Pentraxins ptx3 and sap in innate immunity regulation of inflammation and tissue remodelling
Journal of Hepatology, 2016Co-Authors: Antonio Inforzato, Massimo Messa, Marialuisa Barbagallo, Elena Magrini, Alberto MantovaniAbstract:Summary Pentraxins are a superfamily of fluid phase pattern recognition molecules conserved in evolution and characterized by a cyclic multimeric structure. C-reactive protein (CRP) and serum amyloid P component (SAP) constitute the short pentraxin arm of the superfamily. CRP and SAP are produced in the liver in response to IL-6 and are acute phase reactants in humans and mice respectively. In addition SAP has been shown to affect tissue remodelling and fibrosis by stabilizing all types of amyloid fibrils and by regulating monocyte to fibrocyte differentiation. Pentraxin 3 (PTX3) is the prototype of the long pentraxin arm. Gene targeted mice and genetic and epigenetic studies in humans suggest that PTX3 plays essential non-redundant roles in innate immunity and inflammation as well as in tissue remodelling. Recent studies have revealed the role of PTX3 as extrinsic oncosuppressor, able to tune cancer-related inflammation. In addition, at acidic pH PTX3 can interact with provisional matrix components promoting inflammatory matrix remodelling. Thus acidification during tissue repair sets PTX3 in a tissue remodelling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.
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The long pentraxin PTX3: a paradigm for humoral pattern recognition molecules
Annals of the New York Academy of Sciences, 2013Co-Authors: Alberto Mantovani, Sonia Valentino, Stefania Gentile, Antonio InforzatoAbstract:Pattern recognition molecules (PRMs) are components of the humoral arm of innate immunity; they recognize pathogen-associated molecular patterns (PAMP) and are functional ancestors of antibodies, promoting complement activation, opsonization, and agglutination. In addition, several PRMs have a regulatory function on inflammation. Pentraxins are a family of evolutionarily conserved PRMs characterized by a cyclic multimeric structure. On the basis of structure, Pentraxins have been operationally divided into short and long families. C-reactive protein (CRP) and serum amyloid P component are prototypes of the short pentraxin family, while pentraxin 3 (PTX3) is a prototype of the long Pentraxins. PTX3 is produced by somatic and immune cells in response to proinflammatory stimuli and Toll-like receptor engagement, and it interacts with several ligands and exerts multifunctional properties. Unlike CRP, PTX3 gene organization and regulation have been conserved in evolution, thus allowing its pathophysiological roles to be evaluated in genetically modified animals. Here we will briefly review the general properties of CRP and PTX3 as prototypes of short and long Pentraxins, respectively, emphasizing in particular the functional role of PTX3 as a prototypic PRM with antibody-like properties.
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ptx3 as a paradigm for the interaction of Pentraxins with the complement system
Seminars in Immunology, 2013Co-Authors: Antonio Inforzato, Isabella Barajon, Roberto Leone, Alberto MantovaniAbstract:Abstract Pentraxins are highly conserved components of the humoral arm of innate immunity. They include the short Pentraxins C reactive protein (CRP) and serum amyloid P component (SAP), and the long pentraxin PTX3. These are soluble pattern-recognition molecules that are present in the blood and body fluids, and share the ability to recognize pathogens and promote their disposal. CRP and SAP are produced systemically in the liver while PTX3 is produced locally in a number of tissues, macrophages and neutrophils being major sources of this long pentraxin. Pentraxins interact with components of the classical and lectin pathways of Complement as well as with Complement regulators. In particular, PTX3 recognizes C1q, factor H, MBL and ficolins, where these interactions amplify the repertoire of microbial recognition and effector functions of the Complement system. The complex interaction of Pentraxins with the Complement system at different levels has broad implications for host defence and regulation of inflammation.
Cecilia Garlanda - One of the best experts on this subject based on the ideXlab platform.
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the complement system in aspergillus fumigatus infections and its crosstalk with Pentraxins
FEBS Letters, 2020Co-Authors: Raffaella Parente, Barbara Bottazzi, Andrea Doni, Cecilia Garlanda, Antonio InforzatoAbstract:Aspergillosis is a life-threatening infection mostly affecting immunocompromised individuals and primarily caused by the saprophytic fungus Aspergillus fumigatus. At the host-pathogen interface, both cellular and humoral components of the innate immune system are increasingly acknowledged as essential players in the recognition and disposal of this opportunistic mold. Fundamental hereof is the contribution of the complement system, which deploys all three activation pathways in the battle against A. fumigatus, and functionally cooperates with other soluble pattern recognition molecules, including Pentraxins. In particular, preclinical and clinical observations point to the long pentraxin PTX3 as a nonredundant and complement-dependent effector with protective functions against A. fumigatus. Based on past and current literature, here we discuss how the complement participates in the immune response to this fungal pathogen, and illustrate its crosstalk with the Pentraxins, with a focus on PTX3. Emphasis is placed on the molecular mechanisms underlying such processes, the genetic evidence from human epidemiology, and the translational potential of the currently available knowledge.
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the dual complexity of ptx3 in health and disease a balancing act
Trends in Molecular Medicine, 2016Co-Authors: Elena Magrini, Alberto Mantovani, Cecilia GarlandaAbstract:The humoral arm of innate immunity is complex and includes various molecules that serve as markers of inflammation with complementary characteristics, such as the short Pentraxins C-reactive protein (CRP) and serum amyloid P (SAP) and the long pentraxin PTX3. There is a growing amount of evidence - including mouse and human genetics - that suggests that PTX3 is essential in conferring host resistance against selected pathogens and, moreover, that it plays a dual antagonistic role in the regulation of inflammation. Dissection of such a yin-and-yang role of Pentraxins in immunity and inflammation is timely and significant as it may pave the way for better clinical exploitation against various diseases.
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ptx3 expression in the heart tissues of patients with myocardial infarction and infectious myocarditis
Cardiovascular Pathology, 2011Co-Authors: Manuela Nebuloni, Alberto Mantovani, Fabio Pasqualini, Luca Vago, Pietro Zerbi, Eleonora Lauri, Cecilia GarlandaAbstract:Abstract Introduction The long pentraxin 3 is involved in innate resistance to pathogens, controlling inflammation and extracellular matrix remodeling. Moreover, pentraxin 3 plays a nonredundant role in the regulation of cardiac tissue damage in mice and, recently, it has been proposed as a new candidate marker for acute and chronic heart diseases. However, the actual localization and cellular sources of pentraxin 3 in ischemic and infectious cardiac pathology have not been carefully defined. Methods In this study, using immunohistochemistry, we analyzed pentraxin 3 expression in the heart tissues of patients with acute myocardial infarction at different time points after the ischemic event. In addition, we studied the heart tissues of patients with infectious myocarditis (fungi, bacteria, and protozoa) and patients who died of noncardiac events with normal heart histology. Results In acute myocardial infarction cases, we observed pentraxin 3 localized within and around ischemic lesions. On the contrary, no pentraxin 3 was observed in normal heart areas. In early ischemic lesions, pentraxin 3 was localized primarily in granulocytes; in more advanced acute myocardial infarction, pentraxin 3 positivity was found in the interstitium and in the cytoplasm of macrophages and the endothelium, whereas most granulocytes did not express pentraxin 3, presumably as a consequence of degranulation. In infectious myocarditis, pentraxin 3 was present and localized within and around histological lesions, associated with macrophage, endothelial cell, and, more rarely, myocardiocyte and granulocyte positivities. As observed in acute myocardial infarction patients, no pentraxin 3 staining was found in normal heart areas. Conclusions Thus, neutrophils are an early source of pentraxin 3 in acute myocardial infarction and presumably other inflammatory heart disorders. Subsequently, in acute myocardial infarction and infectious myocarditis, pentraxin 3 is produced by macrophages, the endothelium, and, to a lesser extent, myocardiocytes, and localized in the interstitium.
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role of complement and fcγ receptors in the protective activity of the long pentraxin ptx3 against aspergillus fumigatus
Blood, 2010Co-Authors: Federica Moalli, Barbara Bottazzi, Andrea Doni, Alberto Mantovani, Livija Deban, Teresa Zelante, S Zagarella, Luigina Romani, Cecilia GarlandaAbstract:Pentraxin 3 (PTX3) is a soluble pattern recognition molecule playing a nonredundant role in resistance against Aspergillus fumigatus. The present study was designed to investigate the molecular pathways involved in the opsonic activity of PTX3. The PTX3 N-terminal domain was responsible for conidia recognition, but the full-length molecule was necessary for opsonic activity. The PTX3-dependent pathway of enhanced neutrophil phagocytic activity involved complement activation via the alternative pathway; Fcγ receptor (FcγR) IIA/CD32 recognition of PTX3-sensitized conidia and complement receptor 3 (CR3) activation; and CR3 and CD32 localization to the phagocytic cup. Gene targeted mice (ptx3, FcR common γ chain, C3, C1q) validated the in vivo relevance of the pathway. In particular, the protective activity of exogenous PTX3 against A fumigatus was abolished in FcR common γ chain-deficient mice. Thus, the opsonic and antifungal activity of PTX3 is at the crossroad between complement, complement receptor 3-, and FcγR-mediated recognition. Because short Pentraxins (eg, C-reactive protein) interact with complement and FcγR, the present results may have general significance for the mode of action of these components of the humoral arm of innate immunity.
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Pentraxins: Multifunctional proteins at the interface of innate immunity and inflammation
BioFactors, 2009Co-Authors: Livija Deban, Barbara Bottazzi, Cecilia Garlanda, Yeny Martinez De La Torre, Alberto MantovaniAbstract:Pentraxins are a family of multimeric pattern recognition proteins highly conserved in evolution. On the basis of the primary structure of the protomer, Pentraxins are divided into two groups: short Pentraxins and long Pentraxins. C reactive protein, the first pattern recognition receptor identified, and serum amyloid P component are classic short Pentraxins produced in the liver in response to IL-6. Long Pentraxins, including the prototype PTX3, are expressed in a variety of tissues. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to Toll-like receptor (TLR) engagement and inflammatory cytokines. Through interaction with several ligands, including selected pathogens and apoptotic cells, Pentraxins play a role in complement activation, pathogen recognition and apoptotic cell clearance. In addition, PTX3 is involved in the deposition of extracellular matrix and female fertility. Unlike the classic short Pentraxins CRP and SAP, PTX3 primary sequence and regulation are highly conserved in man and mouse. Thus, gene targeting identified PTX3 (and presumably other members of the family) as multifunctional soluble pattern recognition receptors acting as a nonredundant component of the humoral arm of innate immunity and involved in tuning inflammation, matrix deposition, and female fertility. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.
Barbara Bottazzi - One of the best experts on this subject based on the ideXlab platform.
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the complement system in aspergillus fumigatus infections and its crosstalk with Pentraxins
FEBS Letters, 2020Co-Authors: Raffaella Parente, Barbara Bottazzi, Andrea Doni, Cecilia Garlanda, Antonio InforzatoAbstract:Aspergillosis is a life-threatening infection mostly affecting immunocompromised individuals and primarily caused by the saprophytic fungus Aspergillus fumigatus. At the host-pathogen interface, both cellular and humoral components of the innate immune system are increasingly acknowledged as essential players in the recognition and disposal of this opportunistic mold. Fundamental hereof is the contribution of the complement system, which deploys all three activation pathways in the battle against A. fumigatus, and functionally cooperates with other soluble pattern recognition molecules, including Pentraxins. In particular, preclinical and clinical observations point to the long pentraxin PTX3 as a nonredundant and complement-dependent effector with protective functions against A. fumigatus. Based on past and current literature, here we discuss how the complement participates in the immune response to this fungal pathogen, and illustrate its crosstalk with the Pentraxins, with a focus on PTX3. Emphasis is placed on the molecular mechanisms underlying such processes, the genetic evidence from human epidemiology, and the translational potential of the currently available knowledge.
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The yin-yang of long pentraxin PTX3 in inflammation and immunity.
Immunology Letters, 2014Co-Authors: Kenji Daigo, Alberto Mantovani, Barbara BottazziAbstract:Pentraxins are a family of multimeric proteins characterized by the presence of a pentraxin signature in their C-terminus region. Based on the primary structure, Pentraxins are divided into short and long pentraxin: C-reactive protein (CRP) is the prototype of the short pentraxin subfamily while pentraxin 3 (PTX3) is the prototypic long pentraxin. Despite these two molecules exert similar fundamental actions in the regulation of innate immune and inflammatory responses, several differences exist between CRP and PTX3, including gene organization, protein oligomerization and expression pattern. The pathophysiological roles of PTX3 have been investigated using genetically modified mice since PTX3 gene organization and regulation are well conserved between mouse and human. Such in vivo studies figured out that PTX3 mainly have host-protective effects, even if it could also exert negative effects under certain pathophysiologic conditions. Here we will review the general properties of CRP and PTX3, emphasizing the differences between the two molecules and the regulatory functions exerted by PTX3 in innate immunity and inflammation.
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role of complement and fcγ receptors in the protective activity of the long pentraxin ptx3 against aspergillus fumigatus
Blood, 2010Co-Authors: Federica Moalli, Barbara Bottazzi, Andrea Doni, Alberto Mantovani, Livija Deban, Teresa Zelante, S Zagarella, Luigina Romani, Cecilia GarlandaAbstract:Pentraxin 3 (PTX3) is a soluble pattern recognition molecule playing a nonredundant role in resistance against Aspergillus fumigatus. The present study was designed to investigate the molecular pathways involved in the opsonic activity of PTX3. The PTX3 N-terminal domain was responsible for conidia recognition, but the full-length molecule was necessary for opsonic activity. The PTX3-dependent pathway of enhanced neutrophil phagocytic activity involved complement activation via the alternative pathway; Fcγ receptor (FcγR) IIA/CD32 recognition of PTX3-sensitized conidia and complement receptor 3 (CR3) activation; and CR3 and CD32 localization to the phagocytic cup. Gene targeted mice (ptx3, FcR common γ chain, C3, C1q) validated the in vivo relevance of the pathway. In particular, the protective activity of exogenous PTX3 against A fumigatus was abolished in FcR common γ chain-deficient mice. Thus, the opsonic and antifungal activity of PTX3 is at the crossroad between complement, complement receptor 3-, and FcγR-mediated recognition. Because short Pentraxins (eg, C-reactive protein) interact with complement and FcγR, the present results may have general significance for the mode of action of these components of the humoral arm of innate immunity.
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Pentraxins: Multifunctional proteins at the interface of innate immunity and inflammation
BioFactors, 2009Co-Authors: Livija Deban, Barbara Bottazzi, Cecilia Garlanda, Yeny Martinez De La Torre, Alberto MantovaniAbstract:Pentraxins are a family of multimeric pattern recognition proteins highly conserved in evolution. On the basis of the primary structure of the protomer, Pentraxins are divided into two groups: short Pentraxins and long Pentraxins. C reactive protein, the first pattern recognition receptor identified, and serum amyloid P component are classic short Pentraxins produced in the liver in response to IL-6. Long Pentraxins, including the prototype PTX3, are expressed in a variety of tissues. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to Toll-like receptor (TLR) engagement and inflammatory cytokines. Through interaction with several ligands, including selected pathogens and apoptotic cells, Pentraxins play a role in complement activation, pathogen recognition and apoptotic cell clearance. In addition, PTX3 is involved in the deposition of extracellular matrix and female fertility. Unlike the classic short Pentraxins CRP and SAP, PTX3 primary sequence and regulation are highly conserved in man and mouse. Thus, gene targeting identified PTX3 (and presumably other members of the family) as multifunctional soluble pattern recognition receptors acting as a nonredundant component of the humoral arm of innate immunity and involved in tuning inflammation, matrix deposition, and female fertility. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.
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Pentraxins in innate immunity and inflammation
Novartis Foundation symposium, 2006Co-Authors: Cecilia Garlanda, Barbara Bottazzi, Andrea Doni, Federica Moalli, Livija Deban, Giovanni Salvatori, Rita De Santis, Alessia Cotena, Viriginia Maina, Tania VelizrodriguezAbstract:C-reactive protein, the first innate immunity receptor identified, and serum amyloid P component are classic short Pentraxins produced in the liver. Long Pentraxins, the prototype of which is PTX3, are expressed in a variety of tissues. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to TLR engagement and inflammatory cytokines. PTX3 acts as a functional ancestor of antibodies, recognizing microbes, activating complement, facilitating pathogen recognition by phagocytes, hence playing a non-redundant role in resistance against selected pathogens, in particular in the lung. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor at the crossroads between innate immunity, inflammation, matrix deposition and female fertility.