TY - JOUR
T1 - The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection
AU - Jaillon, Sébastien
AU - Moalli, Federica
AU - Ragnarsdottir, Bryndis
AU - Bonavita, Eduardo
AU - Puthia, Manoj
AU - Riva, Federica
AU - Barbati, Elisa
AU - Nebuloni, Manuela
AU - CvetkoKrajinovic, Lidija
AU - Markotic, Alemka
AU - Valentino, Sonia
AU - Doni, Andrea
AU - Tartari, Silvia
AU - Graziani, Giorgio
AU - Montanelli, Alessandro
AU - Delneste, Yves
AU - Svanborg, Catharina
AU - Garlanda, Cecilia
AU - Mantovani, Alberto
PY - 2014/4/17
Y1 - 2014/4/17
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2014.02.015
DO - 10.1016/j.immuni.2014.02.015
M3 - Article
C2 - 24745336
AN - SCOPUS:84898685230
VL - 40
SP - 621
EP - 632
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 4
ER -