A2 Mechanisms underlying activation and polarisation of inflammatory monocytes and organ-specific regeneration in acute and chronic liver disease
Prof. Dr. med. vet. Hannelore Lotter
Department of Molecular Parasitology
Bernhard Nocht Institute for Tropical Medicine
In the past we were able to identify several immunological mechansims, that are responsible for the liver damage induced by the parasite Entamoeba (E. ) histolytica.
Among other pathways, the activation of the IL-23 / Th17 immune axis is involved, which ultimately leads to an increased recruitment of pro-inflammatory monocytes, which are responsible for the liver damage in the sense of an immunopathology. However, the same monocyte population is protective in the model of Listeria-related liver damage (Project A3). We now want to investigate to what extent these monocytes differ in detail and whether there is more than one population of these cells.
Additionally, we found that certain genes were upregulated in the liver during the regeneration process induced by E. histolytica that might hint towards new mechansims involved in liver regeneration in general. Now we want to investigate these mechanisms in other models for liver damage that are represented within this CRC841.
A02 in 60 SecondsVideoarchivonline seit 28.12.2018
Meyer M, Fehling H, Matthiesen J, Lorenzen S, Schuldt K, Bernin H, Zaruba M, Lender C, Ernst T, Ittrich H, Roeder T, Tannich E, Bruchhaus I, Lotter H
Overexpression of Differentially Expressed Genes Identified in Non-pathogenic and Pathogenic Entamoeba histolytica Clones Allow Identification of New Pathogenicity Factors Involved in Amoebic Liver Abscess Formation
PLoS Pathog. 2016 Aug 30;12(8):e1005853. doi: 10.1371/journal.ppat.1005853. eCollection 2016 Aug.
Bernin H, Fehling H, Marggraff C, Tannich E, Lotter H
The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus
Med Microbiol Immunol. 2016 Aug;205(4):321-32. doi: 10.1007/s00430-016-0449-y. Epub 2016 Feb 20.
Noll J, Helk E, Fehling H, Bernin H, Marggraff C, Jacobs T, Huber S, Pelczar P, Ernst T, Ittrich H, Otto B, Mittrücker HW, Hölscher C, Tacke F, Bruchhaus I, Tannich E, Lotter H
IL-23 promotes immunopathology and prevents IL-13-dependent tissue repair associated with Ly6C(lo) monocytes in Entamoeba histolytica-induced liver damage
J Hepatol. 2016 May;64(5):1147-57. doi: 10.1016/j.jhep.2016.01.013. Epub 2016 Jan 22.
In the first funding period we could show that tissue damage evolves from TNFα-secreting, inflammatory monocytes together with an overwhelming activation of liver resident Kupffer cells. Treatment with testosterone further modulated the immune control thereby augmenting tissue damage.
In the future we want to investigate how factors involved in the lipid metabolism, like the apolipoproteins, regulate an excessive immune activation and elucidate which role the sex hormones would play. We also want to analyse whether an imbalance between immunosuppression and immune activation further contributes to the immunopathology during amebic liver abscess development.