title: The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection.
abstract: Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs.
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy. Electronic address: sebastien.jaillon@humanitasresearch.it.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jaillon
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Moalli
authors.affiliation: Section of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, 22362 Lund, Sweden.
authors.forename: Bryndis
authors.initials: B
authors.lastname: Ragnarsdottir
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonavita
authors.affiliation: Section of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, 22362 Lund, Sweden.
authors.forename: Manoj
authors.initials: M
authors.lastname: Puthia
authors.affiliation: Department of Veterinary Pathology, Hygiene and Public Health, University of Milan, 20133 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Riva
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Barbati
authors.affiliation: Pathology Unit, L. Sacco Department of Clinical Sciences, University of Milan, 20157 Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.affiliation: University Hospital for Infectious Diseases, 10000 Zagreb, Croatia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Cvetko Krajinovic
authors.affiliation: University Hospital for Infectious Diseases, 10000 Zagreb, Croatia.
authors.forename: Alemka
authors.initials: A
authors.lastname: Markotic
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Valentino
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Tartari
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Graziani
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Montanelli
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 892, Centre de Recherche en Cancérologie Nantes-Angers, 44933 Angers, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.affiliation: Section of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, 22362 Lund, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Svanborg
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy; Department of Biotechnology and Translational Medicine, University of Milan, 20089 Rozzano (Milano), Italy. Electronic address: alberto.mantovani@humanitasresearch.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002648:Child; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000150:complications / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis; D011110:Polymorphism, Genetic; D011704:Pyelonephritis / Q000209:etiology / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism*; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*; D013548:Sweden; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014552:Urinary Tract Infections / Q000150:complications / Q000276:immunology*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D053594:Myeloid Differentiation Factor 88; D051192:Receptors, Pattern Recognition; D000683:Serum Amyloid P-Component; D051197:Toll-Like Receptor 4; D000099153:Pentraxins