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

Sébastien Jaillon, Federica Moalli, Bryndis Ragnarsdottir, Eduardo Bonavita, Manoj Puthia, Federica Riva, Elisa Barbati, Manuela Nebuloni, Lidija CvetkoKrajinovic, Alemka Markotic, Sonia Valentino, Andrea Doni, Silvia Tartari, Giorgio Graziani, Alessandro Montanelli, Yves Delneste, Catharina Svanborg, Cecilia Garlanda, Alberto Mantovani

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)621-632
Number of pages12
JournalImmunity
Volume40
Issue number4
DOIs
Publication statusPublished - Apr 17 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    Jaillon, S., Moalli, F., Ragnarsdottir, B., Bonavita, E., Puthia, M., Riva, F., Barbati, E., Nebuloni, M., CvetkoKrajinovic, L., Markotic, A., Valentino, S., Doni, A., Tartari, S., Graziani, G., Montanelli, A., Delneste, Y., Svanborg, C., Garlanda, C., & Mantovani, A. (2014). The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity, 40(4), 621-632. https://doi.org/10.1016/j.immuni.2014.02.015