Defining the immune cascade leading to Nod-like receptor mediated Type 2 immune responses

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Progress for the control of infectious diseases can only be achieved on the basis of our increasing insights into the complex host defence mechanisms. Recent observations have led to the discovery of several host protein families, referred to as pattern recognition molecules including the families of the Toll-like and Nod-like receptors. These host defence proteins specifically detect molecular patterns of pathogens as well as infection-induced physiological changes of infected host cells, suggesting a critical role for their function in regulating antimicrobial immunity. The present project focuses on deciphering the mechanisms of how the mammalian immune system recognizes pathogens leading to the subsequent instruction of long-lived immune responses. In my outlined project I will specifiically aim to charcaterize the immune cascade leading to Nod-like receptor triggered type 2 immune responses and to dissect the soluble mediators involved to induce this immune effector arm. I will (i) define the innate source(s) of IL-4 and IL-13 upon Nod1- and Nod2-mediated pathogen recognition, and examine the involvement of IL-25 and IL-33 for the priming of type 2 immunity, (ii) study the protective role of Nod1- and Nod2-driven type 2 immunity in a gastrointestinal infection model in vivo, and (iii) investigate the involvement of stem cell factor mediated c-kit signalling in Nod1- and Nod2-mediated immune responses. The scientific insights gained from the proposed research program will advance our medical and scientific knowledge, which will enable us to tailor preventive vaccination strategies to combat infectious diseases.