The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection

Immunity. 2014 Apr 17;40(4):621-32. doi: 10.1016/j.immuni.2014.02.015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Cell Line
  • Child
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Escherichia coli / immunology*
  • Escherichia coli Infections / complications
  • Escherichia coli Infections / immunology*
  • 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 / immunology*
  • Neutrophils / microbiology
  • Phagocytosis
  • Polymorphism, Genetic
  • Pyelonephritis / etiology
  • Pyelonephritis / immunology*
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / metabolism*
  • Serum Amyloid P-Component / genetics
  • Serum Amyloid P-Component / metabolism*
  • Sweden
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Urinary Tract Infections / complications
  • Urinary Tract Infections / immunology*

Substances

  • Myeloid Differentiation Factor 88
  • Receptors, Pattern Recognition
  • Serum Amyloid P-Component
  • Toll-Like Receptor 4
  • PTX3 protein
  • C-Reactive Protein