Pregnancy Trained decidua NK cells fight Bacterial Infections more effectively

Rebecca Kotzur ¹ Moriya Gamliel ¹ Shira Kahlon ¹ Debra Goldman-Wohl ² Simcha Yagel ² Ofer Mandelboim ¹

¹The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University Faculty of Medicine, Israel
²The Magda and Richard Hoffman Center for Human Placenta Research, Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Israel

As previously shown decidua NK cells are changed after the first pregnancy and those Pregnancy Trained decidua NK cells found in subsequent pregnancies express different levels of receptors, most prevalent the receptors NKG2C and LILRB1, on their surfaces, characterizing them as a different cell population. This receptor abundance is suspected to alter the reaction of the LILRB1 positive population of PTdNKs towards a more cytotoxic behavior, in contrast to the angiogenic behavior from the LILRB1 negative population. Higher secretion of effector proteins, such as granulysin, involved in lysis of target cells by NK cells in the NKG2C high expressing population was observed emphasizing these findings.

Many bacterial species are involved in adverse pregnancy outcome, for example Listeria monocytogenes, Chlamydia spec., Coxiella burnetti and many more. During this project, we`ll be focusing on Fusobacterium nucleatum, which is not only associated with preterm birth, but also with periodontitis, colon cancer and rheumatoid arthritis, and is suspected to be transmitted hemogenously from other sides of infection to the uterus.

Our hypothesis is that the Pregnancy Trained decidua NK cells are supposed to react upon interaction with a bacterium such as Fusobacterium nucleatum and elicit a higher dose of effectors, like granulysin, in order to eliminate the bacteria and protect the fetus.