P2 From apoptotic cell sensing to an innate memory response: a new aspect of Kupffer cell function

P02_Bosurgi_FP3

Principal Investigator:
Lidia Bosurgi, PhD
I. Medical Center
University Medical Center Hamburg-Eppendorf
Martinistrasse 52
20246 Hamburg

E-Mail: l.bosurgi@uke.de

Participating staff:

Imke Liebold – PhD Student
Madeleine Hamley – PhD Student

Project description
Kupffer cells (KCs) are a population of highly phagocytic, liver tissue-resident macrophages of pre-natal origin. Distinct from hematopoietic-derived macrophages, KCs are long-lived and persist into adulthood. The function of KCs in reference to their long-life span is unknown.

During infection with parasites, such as Schistosoma, which induces an immune response mainly characterized by high release of type 2 cytokines, such as IL-4 and IL-13, macrophages in the liver acquire an anti-inflammatory/tissue healing phenotype. While acquiring this phenotype is essential for the host survival during the initial acute response to the parasite, at the later stage of infection an exacerbated KC anti-inflammatory response is also associated with the development of tissue fibrosis.

Our previous findings have shown that sensing of apoptotic cells is a critical step in the response of macrophages to cytokines such as IL-4 and IL-13. Based on this, and in accordance with the high phagocytic capacity of KCs, here we aim to investigate whether long-lasting sensing of apoptotic cells by KCs can shape their response to type 2 cytokines in the context of Schistosoma infection and confer them an innate memory capacity.
We believe that investigating mechanisms of apoptotic cell sensing by KCs may reveal unexplored therapeutic targets in long-lived liver macrophages and provide crucial insights for long-lasting protection against hepatic infection, while avoiding liver fibrosis.