UPEC KILLS NATURAL KILLER CELLS TO ESTABLISH URINARY TRACT INFECTIONS

Shunit Coppenhagen-Glazer 1 Chamutal Gur 2,3 Ofer Mandelboim 2 Gilad Bachrach 1
1The Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem
2The Lautenberg Center of General and Tumor Immunology, Hebrew University-Hadassah Medical School, IMRIC, Jerusalem
3Internal Medicine Department, Hadassah Medical Center, Jerusalem

Natural killer (NK) cells are important players of the innate immune system. While they are best known for their ability to protect against virus infections and tumors, not much is known about their role in bacterial infections.

Urinary tract infections are commonly caused by Uropathogenic Escherichia coli. Around 50% of all women and 12% of men will experience this infection in their life-time.

Incubation of NK cells with several E. coli strains led to an adherence of the bacteria to the cells at 4oC and to killing of the NK cells by the bacteria at 37oC. The adherence ability was found to be a common trait of various tested E. coli strains however the strains which killed NK cells were associated with urinary tract infections.

Transposon mutagenesis of UPEC CFT073 revealed that type I fimbriae mediates the attachment to NK cells and hemolysinA expressed by UPEC was responsible for killing the NK cells.

We demonstrated, both in vitro and in vivo, that in the absence of hemolysinA NK cells respond directly to the presence of the bacteria by secreting TNFα leading to a reduction in the numbers of colonizing UPEC.

Thus we show that NK cells participate in protection against urinary tract infections and that UPEC evades this immune response by killing the NK cells.








 




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