PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer

Innate immunity includes a cellular and a humoral arm. PTX3 is a fluid-phase pattern recognition molecule conserved in evolution which acts as a key component of humoral innate immunity in infections of fungal, bacterial, and viral origin. PTX3 binds conserved microbial structures and self-components under conditions of inflammation and activates effector functions (complement, phagocytosis). Moreover, it has a complex regulatory role in inflammation, such as ischemia/reperfusion injury and cancer-related inflammation, as well as in extracellular matrix organization and remodeling, with profound implications in physiology and pathology. Finally, PTX3 acts as an extrinsic oncosuppressor gene by taming tumor-promoting inflammation in murine and selected human tumors. Thus evidence suggests that PTX3 is a key homeostatic component at the crossroad of innate immunity, inflammation, tissue repair, and cancer. Dissecting the complexity of PTX3 pathophysiology and human genetics paves the way to diagnostic and therapeutic exploitation.

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An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode

Journal of Experimental Medicine ◽

10.1084/jem.20141268 ◽

2015 ◽

Vol 212 (6) ◽

pp. 905-925 ◽

Cited By ~ 69

Author(s):

Andrea Doni ◽

Tiziana Musso ◽

Diego Morone ◽

Antonio Bastone ◽

Vanessa Zambelli ◽

...

Keyword(s):

Pattern Recognition ◽

Innate Immunity ◽

Tissue Repair ◽

Fluid Phase ◽

Metabolic Adaptation ◽

Fibrin Deposition ◽

Intact Molecule ◽

Pattern Recognition Molecule ◽

Recognition Molecule

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling 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 Humoral Pattern Recognition Molecule PTX3 Is a Key Component of Innate Immunity against Urinary Tract Infection

Immunity ◽

10.1016/j.immuni.2014.02.015 ◽

2014 ◽

Vol 40 (4) ◽

pp. 621-632 ◽

Cited By ~ 66

Author(s):

Sébastien Jaillon ◽

Federica Moalli ◽

Bryndis Ragnarsdottir ◽

Eduardo Bonavita ◽

Manoj Puthia ◽

...

Keyword(s):

Pattern Recognition ◽

Innate Immunity ◽

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Pattern Recognition Molecule ◽

Recognition Molecule

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An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode

The Journal of Cell Biology ◽

10.1083/jcb.2094oia93 ◽

2015 ◽

Vol 209 (4) ◽

pp. 2094OIA93

Author(s):

Andrea Doni ◽

Tiziana Musso ◽

Diego Morone ◽

Antonio Bastone ◽

Vanessa Zambelli ◽

...

Keyword(s):

Pattern Recognition ◽

Tissue Repair ◽

Acidic Microenvironment ◽

Pattern Recognition Molecule ◽

Recognition Molecule

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Re: The Humoral Pattern Recognition Molecule PTX3 is a Key Component of Innate Immunity against Urinary Tract Infection

The Journal of Urology ◽

10.1016/j.juro.2014.10.018 ◽

2015 ◽

Vol 193 (1) ◽

pp. 151-152

Author(s):

Edward M. Schaeffer

Keyword(s):

Pattern Recognition ◽

Innate Immunity ◽

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Pattern Recognition Molecule ◽

Recognition Molecule

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THU0019 INTRON REGIONS OF PIK3AP1 (BCAP) AND SPON2 (SPONDIN-2) GENES ARE DIFFERENTIALLY METHYLATED IN PATIENTS WITH PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS AND ADENITIS (PFAPA) SYNDROME

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5512 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 223.3-223

Author(s):

E. Lovšin ◽

J. Kovac ◽

T. Tesovnik ◽

N. Toplak ◽

D. Perko ◽

...

Keyword(s):

Dna Methylation ◽

Pattern Recognition ◽

Periodic Fever ◽

Aphthous Stomatitis ◽

Extracellular Matrix Protein ◽

Inflammasome Activation ◽

Cervical Adenitis ◽

Pfapa Syndrome ◽

Pattern Recognition Molecule ◽

Recognition Molecule

Background:Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children, often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained.Objectives:We investigated whether a differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA versus a group of healthy young individuals.Methods:A whole epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions. Of identified candidate genes, two with most significantly different methylation leves were further evaluated with methylation specific restriction enzymes coupled with qPCR (MSRE-qPCR).Results:The analysis showed thatPIK3AP1andSPON2intronic gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved as a quick, reliable and cost-effective method to confirm results from MeDIP and MBD.Conclusion:Our findings indicate that B cell adapter protein (BCAP) as PI3K binding inhibitor of inflammation and spondin-2 (SPON2) as a pattern recognition molecule and integrin ligand could play a role in etiology of PFAPA. Their role and impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation.References:[1]Wekell P. Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome – PFAPA syndrome. Press Medicale [Internet]. 2019;48(1):e77–87. Available from:https://doi.org/10.1016/j.lpm.2018.08.016[2]K. Theodoropoulou, F. Vanoni, and M. Hofer, “Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis,”Curr. Rheumatol. Rep., vol. 18:18, 2016.[3]Carpentier SJ, Ni M, Duggan JM, James RG, Cookson BT, Hamerman JA. The signaling adaptor BCAP inhibits NLRP3 and NLRC4 inflammasome activation in macrophages through interactions with Flightless-1. Sci Signal. 2019;12(581).[4]He YW, Li H, Zhang J, Hsu CL, Lin E, Zhang N, et al. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nat Immunol. 2004;5(1):88–97.Disclosure of Interests:None declared

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Studies of the Pattern Recognition Molecule H-ficolin

Journal of Biological Chemistry ◽

10.1074/jbc.m111.301044 ◽

2012 ◽

Vol 287 (11) ◽

pp. 8071-8081 ◽

Cited By ~ 25

Author(s):

Rikke M. Zacho ◽

Lisbeth Jensen ◽

Randi Terp ◽

Jens C. Jensenius ◽

Steffen Thiel

Keyword(s):

Pattern Recognition ◽

Pattern Recognition Molecule ◽

Recognition Molecule

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ON VASCULAR STENOSIS, RESTENOSIS AND MANNOSE BINDING LECTIN

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-6720201600010015 ◽

2016 ◽

Vol 29 (1) ◽

pp. 57-59 ◽

Cited By ~ 1

Author(s):

Barbara Stadler KAHLOW ◽

Rodrigo Araldi NERY ◽

Thelma L SKARE ◽

Carmen Australia Paredes Marcondes RIBAS ◽

Gabriela Piovezani Ramos ◽

...

Keyword(s):

Innate Immunity ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Mannose Binding Lectin ◽

Mannose Binding ◽

Vascular Stenosis ◽

Micro Organisms ◽

The Complement System ◽

Binding Lectin

Mannose binding lectin is a lectin instrumental in the innate immunity. It recognizes carbohydrate patterns found on the surface of a large number of pathogenic micro-organisms, activating the complement system. However, this protein seems to increase the tissue damage after ischemia. In this paper is reviewed some aspects of harmful role of the mannose binding lectin in ischemia/reperfusion injury.

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Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

10.1101/2021.06.07.21258350 ◽

2021 ◽

Author(s):

Matteo Stravalaci ◽

Isabel Pagani ◽

Elvezia Maria Paraboschi ◽

Mattia Pedotti ◽

Andrea Doni ◽

...

Keyword(s):

Pattern Recognition ◽

Innate Immunity ◽

Disease Severity ◽

Fluid Phase ◽

Systematic Investigation ◽

In Vitro Models ◽

Lectin Pathway ◽

Mannose Binding ◽

Binding Lectin

The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in COVID-19. The present study was designed to conduct a systematic investigation of the interaction of humoral fluid phase pattern recognition molecules (PRM) with SARS-CoV-2. Out of 10 PRM tested, the long pentraxin PTX3 and Mannose Binding Lectin (MBL) bound the viral Nucleoprotein and Spike, respectively. MBL bound trimeric Spike, including that of variants of concern, in a glycan-dependent way and inhibited SARS-CoV-2 in three in vitro models. Moreover, upon binding to Spike, MBL activated the lectin pathway of complement activation. Genetic polymorphisms at the MBL locus were associated with disease severity. These results suggest that selected humoral fluid phase PRM can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.

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