1. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection.
- Author
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Jaillon S, Moalli F, Ragnarsdottir B, Bonavita E, Puthia M, Riva F, Barbati E, Nebuloni M, Cvetko Krajinovic L, Markotic A, Valentino S, Doni A, Tartari S, Graziani G, Montanelli A, Delneste Y, Svanborg C, Garlanda C, and Mantovani A
- Subjects
- Animals, C-Reactive Protein genetics, Cell Line, Child, DNA Mutational Analysis, Disease Models, Animal, Escherichia coli Infections complications, Female, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Mice, Mice, Inbred C57BL, Mice, Knockout, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 metabolism, Neutrophils microbiology, Phagocytosis, Polymorphism, Genetic, Pyelonephritis etiology, Receptors, Pattern Recognition genetics, Serum Amyloid P-Component genetics, Sweden, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Urinary Tract Infections complications, C-Reactive Protein metabolism, Escherichia coli immunology, Escherichia coli Infections immunology, Neutrophils immunology, Pyelonephritis immunology, Receptors, Pattern Recognition metabolism, Serum Amyloid P-Component metabolism, Urinary Tract Infections immunology
- 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., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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