Dec. 13, 2018 from 2 p.m. to 3 p.m.
Hess 2nd Floor – Seminar Room A
Hess Center for Science & Medicine
1470 Madison Avenue
- Anette Christ, PhD
- UMass Medical School
- Department of Medicine
- Division for Infectious Diseases and Immunology
- Institute for Innate Immunity Biomedical Center
- University Hospital Bonn, Germany
Abstract: Sustained epigenetic reprogramming of innate immune cells in
response to pathogens, termed ’trained immunity’ or ’innate immune memory’,
beneficially converts cellular functionality to protect from secondary infections.
However, inappropriate activation of immunological imprinting mediated by
’trained immunity’ may contribute to reinforced immune responses in
inflammatory diseases, such as type 2 diabetes, obesity and cardiovascular
diseases (CVDs). Given the above hypothesis, we previously investigated
whether a hyperlipidemic environment can considerably modify innate immune
cell gene signatures, thus evoking a condition of continuous immune cell
activation. Using the Ldlr-/- hypercholesterolemia mouse model, we discovered
that a short period of Western diet (WD) feeding resulted in a transient systemic
inflammatory response, yet induces long-lasting transcriptomic and epigenomic
reprogramming of myeloid cells, which led to immune cell hyper-responsiveness
upon subsequent immune stimulation. These data suggest that WD is capable of
inducing trained immunity and that the immune system misinterprets WD as a
pathogenic infection. Recently, several reports have documented the
detrimental effect of ‘Western-type’ diets on gut microbial composition, the
impact on local and systemic immune responses and a potential link to CVDs.
Alltogether, these findings still raise the questions how and on which level
dietary intake, NLRP3 activation, subsequent IL-1 signaling and long-term
hematopoietic myeloid progenitor reprogramming are interrelated.
At the moment, we are assessing, if WD-induced alterations in the intestinal
microbiome and microbiome-associated metabolites are impacting the cellular
metabolism and signaling pathways in tissue-resident macrophage subsets in
different metabolic organs, as well as in hematopoietic stem cells, thus leading
to sustained epigenetic modifications. Beside, we are examining, whether the
WD-induced myeloid progenitor reprogramming can be modulated/ reversed by
epigenetic enzyme inhibitors.