Identification of Host Immune Mechanisms Involved in Enterococcal Infections

Author/s :Scheb-Wetzel, Matthias Alexander
First examiner :Apl. Prof. Dr. Rohde, Manfred
Institute / Publisher :Helmholtz-Zentrum für Infektionsforschung (HZI)
Faculty :02 - Life Sciences
Date :2016-11-18
Documents :
Size :125 S.
Language :english
Abstract :Enterococcus faecalis has emerged as the third most common cause of life-threatening bacterial nosocomial infections in the US and in Europe. The knowledge of how enterococci interact with the host immune system is still very limited.
The aim of this thesis was to explore the role of so far neglected sentinel cells of the innate immune system like mast cells (MC) and dendritic cells (DC). Also the endothelial barrier represents an important first counterpart with major immunomodulatory functions in the response to E. faecalis infections.
Here it could be shown that MCs have a protective and critical role in the control of E. faecalis growth based on extracellular processes; first, by the formation of so called mast cells extracellular traps (MCETs) and second by the release of pre-stored antimicrobial peptides like the cathelicidin LL-37, which could be confirmed as the antimicrobial agent responsible to induce cell wall stress and vesicle formation on the surface of E. faecalis. Furthermore the importance of the TLR/MyD88 signaling pathway in the response of MCs to E. faecalis was confirmed using MyD88 or TLR2 deficient MCs.
In comparison to MCs, DCs actively phagocytize and kill E. faecalis and create an inflammatory milieu consisting of immunomodulatory molecules like IL-12, KC or MIP-2 underlining the modulatory function of these cells. The TLR/MyD88 pathway could also be determined to be important for DC maturation and the release of mediators underlining the key role of this pattern recognition receptor-mediated pathway in the immune response to enterococci.
Entering the blood stream, E. faecalis faces the endothelial barrier. Endothelial cells are an essential source of cytokine and chemokine production during bacterial infection and additionally, it is involved in a process called leukocyte extravasation which is mediated by the expression of endothelial surface receptors like E-selectin, ICAM-1 and VCAM-1.
This study provided for the first time evidence, that E. faecalis is able to interfere with this pathway and therefore blocking the adhesion and transmigration of leukocytes through the endothelial barrier into deeper tissue. Moreover, a diminished IL-8 response indicates the ability for E. faecalis to manipulate the responses of the endothelial barrier. Taken together this work is shedding light on the complex interplay between E. faecalis and the host innate immune response.
Subject :571 Physiology and related subjects
616 Diseases
Type :dissertation
Format :text/document
URN:NBN :urn:nbn:de:gbv:084-16112911376
Permalink :http://www.digibib.tu-bs.de/?docid=00064089