Crosstalk between TLR4 and NOD1/2 in kidney transplantation

immunology transplantation nephrology

E.G.D. Stribos
dr R. Mutsaers
dr P. Olinga

Nature of the research:
Translational and fundamental research in the field of nephrology

Fields of study:
immunology nephrology

Background / introduction
Activation of the innate immunity through pattern recognition receptors (PRRs) has been postulated to play an important role in the inflammatory response following kidney transplantation. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) orchestrate the inflammatory response to microbial pathogens called pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). It has been postulated that both pathways interact with each other; however the exact mechanisms of this synergy is unknown.
Research question / problem definition
We will study the crosstalk between TLR4 and NOD1/2 using precision-cut kidney slices (PCKS). Refer to the figure for the preparation of PCKS (figure from Stribos et al). For this technique we use human or mouse kidney tissue which is cut in very thin slices. Subsequently the slices are incubated in medium. The student will get the opportunity to learn a multitude of lab techniques, analyze the obtained data and plan further experiments depending on the results.
(1) Stribos EG, Luangmonkong T, Leliveld AM, de Jong IJ, van Son WJ, Hillebrands JL, et al. Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis. Transl Res 2015 Nov 25.
(2) Sun J, Ding Y. NOD2 agonist promotes the production of inflammatory cytokines in VSMC in synergy with TLR2 and TLR4 agonists. ScientificWorldJournal 2012;2012:607157.
(3) Fritz JH, Girardin SE, Fitting C, Werts C, Mengin-Lecreulx D, Caroff M, et al. Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and NOD1- and NOD2-activating agonists. Eur J Immunol 2005 Aug;35(8):2459-2470.
(4) Foley NM, Wang J, Redmond HP, Wang JH. Current knowledge and future directions of TLR and NOD signaling in sepsis. Mil Med Res 2015 Jan 7;2:1-014-0029-7. eCollection 2015.
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