Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells

Chamutal Gur; Shunit Coppenhagen-Glazer; Shilo Rosenberg; Rachel Yamin; Jonatan Enk; Ariella Glasner; Yotam Bar-On; Omer Fleissig; Ronit Naor; Jawad Abed; Dror Mevorach; Zvi Granot; Gilad Bachrach; Ofer Mandelboim

doi:10.1016/j.chom.2013.11.004

Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells

Chamutal Gur, Shunit Coppenhagen-Glazer, Shilo Rosenberg, Rachel Yamin, Jonatan Enk, Ariella Glasner, Yotam Bar-On, Omer Fleissig, Ronit Naor, Jawad Abed, Dror Mevorach, Zvi Granot, Gilad Bachrach^*, Ofer Mandelboim

^*Corresponding author for this work

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

55 Scopus citations

Abstract

Uropathogenic Escherichia coli (UPEC) are a common cause of urinary tract infections (UTIs) in humans. While the importance of natural killer (NK) cells in innate immune protection against tumors and viral infections is well documented, their role in defense against bacterial infections is still emerging, and their involvement in UPEC-mediated UTI is practically unknown. Using a systematic mutagenesis approach, we found that UPEC adheres to NK cells primarily via its type I fimbriae and employs its hemolysinA toxin to kill NK cells. In the absence of hemolysinA, NK cells directly respond to the bacteria and secrete the cytokine TNF-α, which results in decreased bacterial numbers in vitro and reduction of bacterial burden in the infected bladders. Thus, NK cells control UPEC via TNF-α production, which UPEC counteracts by hemolysinA-mediated killing of NK cells, representing a previously unrecognized host defense and microbial counterattack mechanism in the context of UTI.

Original language	English
Pages (from-to)	664-674
Number of pages	11
Journal	Cell Host and Microbe
Volume	14
Issue number	6
DOIs	https://doi.org/10.1016/j.chom.2013.11.004
State	Published - 11 Dec 2013

Bibliographical note

Funding Information:
This study was supported by the Advanced ERC grant, by The Israeli Science Foundation, by The Israeli- I-CORE, by the GIF Foundation, and by The ICRF Professorship Grant (all to O.M.) and by the Israeli Science Foundation (to G.B.). The work was also supported by the Israeli Science Foundation (to C.G.). O.M. is a Crown Professor of Molecular Immunology. C.G. is supported by the Foulkes Foundation. The authors would like to thank Professors Hirotada Mori and Toru Nakayashiki for useful discussion. The authors would also like to thank Professor Saul Burdman, who kindly supplied the pMODkan plasmid. The pGNH404 plasmid was a gift from Professor Agneta Richter-Dahlfors. Bacterial strains CFT073, UPEC76, CFT073ON, CFT073OFF, and CFT fim/pap were from Professor Harry Mobley’s collection. The authors thank Professor Ilan Rosenshine for the EPEC E2348/69 strain and Professor Nahum Shpigel for the UTI89 and UTI536 strains. The authors are grateful to the EM Unit of Core Research Facility of the Faculty of Medicine, The Hebrew University Jerusalem, for assistance with electron microscopy.

Access to Document

10.1016/j.chom.2013.11.004

Cite this

Gur, C., Coppenhagen-Glazer, S., Rosenberg, S., Yamin, R., Enk, J., Glasner, A., Bar-On, Y., Fleissig, O., Naor, R., Abed, J., Mevorach, D., Granot, Z., Bachrach, G., & Mandelboim, O. (2013). Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells. Cell Host and Microbe, 14(6), 664-674. https://doi.org/10.1016/j.chom.2013.11.004

@article{93382c00f7b849458ed8e6f16f5439d0,

title = "Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells",

abstract = "Uropathogenic Escherichia coli (UPEC) are a common cause of urinary tract infections (UTIs) in humans. While the importance of natural killer (NK) cells in innate immune protection against tumors and viral infections is well documented, their role in defense against bacterial infections is still emerging, and their involvement in UPEC-mediated UTI is practically unknown. Using a systematic mutagenesis approach, we found that UPEC adheres to NK cells primarily via its type I fimbriae and employs its hemolysinA toxin to kill NK cells. In the absence of hemolysinA, NK cells directly respond to the bacteria and secrete the cytokine TNF-α, which results in decreased bacterial numbers in vitro and reduction of bacterial burden in the infected bladders. Thus, NK cells control UPEC via TNF-α production, which UPEC counteracts by hemolysinA-mediated killing of NK cells, representing a previously unrecognized host defense and microbial counterattack mechanism in the context of UTI.",

author = "Chamutal Gur and Shunit Coppenhagen-Glazer and Shilo Rosenberg and Rachel Yamin and Jonatan Enk and Ariella Glasner and Yotam Bar-On and Omer Fleissig and Ronit Naor and Jawad Abed and Dror Mevorach and Zvi Granot and Gilad Bachrach and Ofer Mandelboim",

note = "Funding Information: This study was supported by the Advanced ERC grant, by The Israeli Science Foundation, by The Israeli- I-CORE, by the GIF Foundation, and by The ICRF Professorship Grant (all to O.M.) and by the Israeli Science Foundation (to G.B.). The work was also supported by the Israeli Science Foundation (to C.G.). O.M. is a Crown Professor of Molecular Immunology. C.G. is supported by the Foulkes Foundation. The authors would like to thank Professors Hirotada Mori and Toru Nakayashiki for useful discussion. The authors would also like to thank Professor Saul Burdman, who kindly supplied the pMODkan plasmid. The pGNH404 plasmid was a gift from Professor Agneta Richter-Dahlfors. Bacterial strains CFT073, UPEC76, CFT073ON, CFT073OFF, and CFT fim/pap were from Professor Harry Mobley{\textquoteright}s collection. The authors thank Professor Ilan Rosenshine for the EPEC E2348/69 strain and Professor Nahum Shpigel for the UTI89 and UTI536 strains. The authors are grateful to the EM Unit of Core Research Facility of the Faculty of Medicine, The Hebrew University Jerusalem, for assistance with electron microscopy. ",

year = "2013",

month = dec,

day = "11",

doi = "10.1016/j.chom.2013.11.004",

language = "אנגלית",

volume = "14",

pages = "664--674",

journal = "Cell Host and Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "6",

}

Gur, C, Coppenhagen-Glazer, S, Rosenberg, S, Yamin, R, Enk, J, Glasner, A, Bar-On, Y, Fleissig, O, Naor, R, Abed, J, Mevorach, D, Granot, Z , Bachrach, G & Mandelboim, O 2013, 'Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells', Cell Host and Microbe, vol. 14, no. 6, pp. 664-674. https://doi.org/10.1016/j.chom.2013.11.004

TY - JOUR

T1 - Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells

AU - Gur, Chamutal

AU - Coppenhagen-Glazer, Shunit

AU - Rosenberg, Shilo

AU - Yamin, Rachel

AU - Enk, Jonatan

AU - Glasner, Ariella

AU - Bar-On, Yotam

AU - Fleissig, Omer

AU - Naor, Ronit

AU - Abed, Jawad

AU - Mevorach, Dror

AU - Granot, Zvi

AU - Bachrach, Gilad

AU - Mandelboim, Ofer

N1 - Funding Information: This study was supported by the Advanced ERC grant, by The Israeli Science Foundation, by The Israeli- I-CORE, by the GIF Foundation, and by The ICRF Professorship Grant (all to O.M.) and by the Israeli Science Foundation (to G.B.). The work was also supported by the Israeli Science Foundation (to C.G.). O.M. is a Crown Professor of Molecular Immunology. C.G. is supported by the Foulkes Foundation. The authors would like to thank Professors Hirotada Mori and Toru Nakayashiki for useful discussion. The authors would also like to thank Professor Saul Burdman, who kindly supplied the pMODkan plasmid. The pGNH404 plasmid was a gift from Professor Agneta Richter-Dahlfors. Bacterial strains CFT073, UPEC76, CFT073ON, CFT073OFF, and CFT fim/pap were from Professor Harry Mobley’s collection. The authors thank Professor Ilan Rosenshine for the EPEC E2348/69 strain and Professor Nahum Shpigel for the UTI89 and UTI536 strains. The authors are grateful to the EM Unit of Core Research Facility of the Faculty of Medicine, The Hebrew University Jerusalem, for assistance with electron microscopy.

PY - 2013/12/11

Y1 - 2013/12/11

N2 - Uropathogenic Escherichia coli (UPEC) are a common cause of urinary tract infections (UTIs) in humans. While the importance of natural killer (NK) cells in innate immune protection against tumors and viral infections is well documented, their role in defense against bacterial infections is still emerging, and their involvement in UPEC-mediated UTI is practically unknown. Using a systematic mutagenesis approach, we found that UPEC adheres to NK cells primarily via its type I fimbriae and employs its hemolysinA toxin to kill NK cells. In the absence of hemolysinA, NK cells directly respond to the bacteria and secrete the cytokine TNF-α, which results in decreased bacterial numbers in vitro and reduction of bacterial burden in the infected bladders. Thus, NK cells control UPEC via TNF-α production, which UPEC counteracts by hemolysinA-mediated killing of NK cells, representing a previously unrecognized host defense and microbial counterattack mechanism in the context of UTI.

AB - Uropathogenic Escherichia coli (UPEC) are a common cause of urinary tract infections (UTIs) in humans. While the importance of natural killer (NK) cells in innate immune protection against tumors and viral infections is well documented, their role in defense against bacterial infections is still emerging, and their involvement in UPEC-mediated UTI is practically unknown. Using a systematic mutagenesis approach, we found that UPEC adheres to NK cells primarily via its type I fimbriae and employs its hemolysinA toxin to kill NK cells. In the absence of hemolysinA, NK cells directly respond to the bacteria and secrete the cytokine TNF-α, which results in decreased bacterial numbers in vitro and reduction of bacterial burden in the infected bladders. Thus, NK cells control UPEC via TNF-α production, which UPEC counteracts by hemolysinA-mediated killing of NK cells, representing a previously unrecognized host defense and microbial counterattack mechanism in the context of UTI.

UR - http://www.scopus.com/inward/record.url?scp=84890305860&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2013.11.004

DO - 10.1016/j.chom.2013.11.004

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 24331464

AN - SCOPUS:84890305860

SN - 1931-3128

VL - 14

SP - 664

EP - 674

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 6

ER -

Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this