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.
authors: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel; Internal Medicine Department, Hadassah Medical Center, Jerusalem 91120, Israel.
authors: Chamutal
authors: C
authors: Gur
authors: The Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Shunit
authors: S
authors: Coppenhagen-Glazer
authors: Urology Department, Hadassah Medical Center, Jerusalem 91120, Israel.
authors: Shilo
authors: S
authors: Rosenberg
authors: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
authors: Rachel
authors: R
authors: Yamin
authors: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
authors: Jonatan
authors: J
authors: Enk
authors: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
authors: Ariella
authors: A
authors: Glasner
authors: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
authors: Yotam
authors: Y
authors: Bar-On
authors: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel; The Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Omer
authors: O
authors: Fleissig
authors: The Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Ronit
authors: R
authors: Naor
authors: The Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel.
authors: Jawad
authors: J
authors: Abed
authors: Internal Medicine Department, Hadassah Medical Center, Jerusalem 91120, Israel.
authors: Dror
authors: D
authors: Mevorach
authors: Department of Developmental Biology and Cancer Research, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
authors: Zvi
authors: Z
authors: Granot
authors: The Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem 91120, Israel. Electronic address: giladba@ekmd.huji.ac.il.
authors: Gilad
authors: G
authors: Bachrach
authors: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel. Electronic address: oferm@ekmd.huji.ac.il.
authors: Ofer
authors: O
authors: Mandelboim
mesh_terms: D000818:Animals; D058491:Bacterial Load; D002470:Cell Survival; D002478:Cells, Cultured; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D056689:Uropathogenic Escherichia coli / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors