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

Cell Host & Microbe
Chamutal GurOfer Mandelboim

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.

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Citations

May 29, 2015·Proceedings of the National Academy of Sciences of the United States of America·Nicholas P GreeneVassilis Koronakis
Dec 2, 2015·The Journal of Infectious Diseases·Zhengguo ZhangSudhanshu Bhushan
Aug 4, 2015·Medical Microbiology and Immunology·Liang PengXiao-Yan Deng
Sep 22, 2015·Nature Reviews. Immunology·Soman N Abraham, Yuxuan Miao
Mar 31, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Orit BerhaniOfer Mandelboim
Nov 1, 2016·Infection and Immunity·Carrie L ShafferMaria Hadjifrangiskou
Mar 29, 2019·PLoS Biology·Amit BenbenishtyPablo Blinder
Nov 24, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Nader ShaikhTimothy R Shope
Jul 15, 2020·Nature Reviews. Urology·Livia Lacerda Mariano, Molly A Ingersoll
Jun 15, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Christina ChingBrian Becknell
Oct 14, 2017·Scientific Reports·Ariella GlasnerOfer Mandelboim
Sep 16, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ariella GlasnerOfer Mandelboim
Jul 15, 2017·Frontiers in Microbiology·Paul LemireMariela Segura
Sep 26, 2019·Frontiers in Microbiology·Víctor M Luna-PinedaJuan Xicohtencatl-Cortes
Mar 26, 2016·Cancer Research·Ye JinJun Yu
Mar 25, 2019·The Journal of Pediatrics·Nader ShaikhTimothy R Shope
Apr 27, 2021·Current Opinion in Infectious Diseases·Jawid Nazir Ahmad, Peter Sebo
Nov 16, 2021·American Journal of Physiology. Renal Physiology·Nicolas MontalbettiMarcelo D Carattino

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