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

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

Author information

1
Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy. Electronic address: sebastien.jaillon@humanitasresearch.it.
2
Humanitas Clinical Research Center, via Manzoni 56, 20089 Rozzano (Milano), Italy.
3
Section of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, 22362 Lund, Sweden.
4
Department of Veterinary Pathology, Hygiene and Public Health, University of Milan, 20133 Milan, Italy.
5
Pathology Unit, L. Sacco Department of Clinical Sciences, University of Milan, 20157 Milan, Italy.
6
University Hospital for Infectious Diseases, 10000 Zagreb, Croatia.
7
Institut National de la Santé et de la Recherche Médicale, Unité 892, Centre de Recherche en Cancérologie Nantes-Angers, 44933 Angers, France.
8
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.

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.

PMID:
24745336
DOI:
10.1016/j.immuni.2014.02.015
[Indexed for MEDLINE]
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