A2 Mechanisms underlying activation and polarisation of inflammatory monocytes and organ-specific regeneration in acute and chronic liver disease


Principal Investigator:
Prof. Dr. med. vet. Hannelore Lotter
Department of Molecular Parasitology
Bernhard Nocht Institute for Tropical Medicine
Bernhard-Nocht-Str. 74
20359 Hamburg
Tel.: +49-40-42818-475
Fax: +49-40-42818-512
E-Mail: lotter@bni-hamburg.de

Project description

Infections with the parasite Entamoeba histolytica can result in a massive destruction of the liver tissue, the amebic liver abscess. The disease shows a sexual dimorphism with a marked bias towards adult men. So far, immunological backgrounds that are responsible for this sex dimorphism remain to be elusive.

From the animal model we know that a dysregulation of the immune response in terms of an immunopathology underlies disease development and assume, that the interaction of sex hormones with the lipid metabolism plays a causative role in the development of amebic liver abscess.

A2 in 60 SecondsVideoarchiv

online seit 23.06.2014

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.

Related news:

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.