Protease-activated receptor 2 facilitates bacterial dissemination in pneumococcal pneumonia

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Protease-activated receptor 2 facilitates bacterial dissemination in pneumococcal pneumonia. / van den Boogaard, Florry E.; Brands, Xanthe; Duitman, JanWillem et al.

In: Journal of infectious diseases, Vol. 217, No. 9, 2018, p. 1462-1471.

Research output: Contribution to journal › Article › Academic › peer-review

BibTeX

@article{f2cbcdcc27c946998c09dda0864477b5,

title = "Protease-activated receptor 2 facilitates bacterial dissemination in pneumococcal pneumonia",

abstract = "Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. Protease-activated receptor 2 (PAR2) is expressed by different cell types in the lungs and can mediate inflammatory responses. We sought to determine the role of PAR2 during pneumococcal pneumonia. Pneumococcal pneumonia or sepsis was induced in wild-type and PAR2 knock-out (Par2−/−) mice by infection with viable S. pneumoniae. Par2−/− mice demonstrated improved host defense, a largely preserved lung barrier integrity, and reduced mortality during pneumococcal pneumonia. PAR2 deficiency did not influence bacterial growth after intravenous infection. Inhibition of the endogenous PAR2 activating proteases tissue factor/factor VIIa or tryptase did not impact on bacterial burdens during pneumonia. In a PAR2 reporter cell line it was demonstrated that S. pneumoniae-derived proteases are able to cleave PAR2. These results show that S. pneumoniae is able to cleave and exploit PAR2 to disseminate systemically from the airways.",

author = "{van den Boogaard}, {Florry E.} and Xanthe Brands and JanWillem Duitman and {de Stoppelaar}, {Sacha F.} and Borensztajn, {Keren S.} and Roelofs, {Joris J. T. H.} and Hollenberg, {Morley D.} and Spek, {C. Arnold} and Schultz, {Marcus J.} and {van {\textquoteleft}t Veer}, Cornelis and {van der Poll}, Tom",

year = "2018",

doi = "10.1093/infdis/jiy010",

language = "English",

volume = "217",

pages = "1462--1471",

journal = "Journal of infectious diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "9",

}

RIS

TY - JOUR

T1 - Protease-activated receptor 2 facilitates bacterial dissemination in pneumococcal pneumonia

AU - van den Boogaard, Florry E.

AU - Brands, Xanthe

AU - Duitman, JanWillem

AU - de Stoppelaar, Sacha F.

AU - Borensztajn, Keren S.

AU - Roelofs, Joris J. T. H.

AU - Hollenberg, Morley D.

AU - Spek, C. Arnold

AU - Schultz, Marcus J.

AU - van ‘t Veer, Cornelis

AU - van der Poll, Tom

PY - 2018

Y1 - 2018

N2 - Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. Protease-activated receptor 2 (PAR2) is expressed by different cell types in the lungs and can mediate inflammatory responses. We sought to determine the role of PAR2 during pneumococcal pneumonia. Pneumococcal pneumonia or sepsis was induced in wild-type and PAR2 knock-out (Par2−/−) mice by infection with viable S. pneumoniae. Par2−/− mice demonstrated improved host defense, a largely preserved lung barrier integrity, and reduced mortality during pneumococcal pneumonia. PAR2 deficiency did not influence bacterial growth after intravenous infection. Inhibition of the endogenous PAR2 activating proteases tissue factor/factor VIIa or tryptase did not impact on bacterial burdens during pneumonia. In a PAR2 reporter cell line it was demonstrated that S. pneumoniae-derived proteases are able to cleave PAR2. These results show that S. pneumoniae is able to cleave and exploit PAR2 to disseminate systemically from the airways.

AB - Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. Protease-activated receptor 2 (PAR2) is expressed by different cell types in the lungs and can mediate inflammatory responses. We sought to determine the role of PAR2 during pneumococcal pneumonia. Pneumococcal pneumonia or sepsis was induced in wild-type and PAR2 knock-out (Par2−/−) mice by infection with viable S. pneumoniae. Par2−/− mice demonstrated improved host defense, a largely preserved lung barrier integrity, and reduced mortality during pneumococcal pneumonia. PAR2 deficiency did not influence bacterial growth after intravenous infection. Inhibition of the endogenous PAR2 activating proteases tissue factor/factor VIIa or tryptase did not impact on bacterial burdens during pneumonia. In a PAR2 reporter cell line it was demonstrated that S. pneumoniae-derived proteases are able to cleave PAR2. These results show that S. pneumoniae is able to cleave and exploit PAR2 to disseminate systemically from the airways.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050771232&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/29415278

U2 - 10.1093/infdis/jiy010

DO - 10.1093/infdis/jiy010

M3 - Article

C2 - 29415278

VL - 217

SP - 1462

EP - 1471

JO - Journal of infectious diseases

JF - Journal of infectious diseases

SN - 0022-1899

IS - 9

ER -

ID: 4591387

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