Our immune response is much stronger regulated by environmental factors than was known so far. Scientists spearheaded from Radboud University and Radboud University Medical Center, Cambridge Universities and the Welcome Trust Sanger Institute uncovered epigenetic programs that distinguish tolerant and trained macrophages. These findings improve our understanding of how the immune system keeps infection at bay and provide invaluable resources to manipulate the immune system, Science reports.
This study is one of three BLUEPRINT papers published in Science. The BLUEPRINT project aims at deciphering the epigenomes of more than 100 different types of blood cells. It is one of the two first so-called European high impact research initiatives
Trained immunity
In individuals with infection, activation of monocytes and differentiation of macrophages can differ depending of the type of pathogen and infection. During severe infections and sepsis, monocytes and macrophages undergo a period of reduced activity or so called "tolerance". During this period the cells react much less efficiently to invading pathogens and the host is more prone to infections. In contrast, during other types of infections, and especially after vaccinations such as measles, the monocytes and macrophages react more strongly to pathogens, a process termed "trained immunity". This represents a de facto memory of innate immunity.
A study in Science by Saeed et al demonstrates that distinct epigenetic programs execute immune tolerance and trained immunity, and describes novel specific pathways that induce these processes.
Environmental factors more important than expected
"The immune response of the host is much stronger regulated by environmental factors than we thought" remarked Mihai Netea who is Professor of Experimental Medicine at Radboud University Medical Center. He continued "We were surprised to see how different the blueprints of monocytes and macrophages were. It shows the strong effects of the different body compartments, setting up the monocytes to act quickly to an invading pathogen, whilst macrophages that reside in tissues like skin and gut are instructed to be more tolerant."
BLUEPRINT: Epigenetics of blood
After the human genome was deciphered, it became apparent that knowing the DNA code and how it is organised in chromosomes is insufficient to understand how the code is used to determine the identity of cells. There are lots of different types of cells in the body and each cell has the same DNA content, yet cells differ greatly in their appearance and function. They change in response to outside signals and as a consequence of aging and their altered states underlie diseases. Thus, the way the genetic information is used differs between each type of cell and this difference is in part determined by how DNA is packaged in chromosomes. Epigenetics aims at unravelling this packaging through structural adaptation of chromosomes which determines how DNA elements are regulated. The newly gained layers of information, which are unique to a particular type of cells are placed on "top of the genome" to form a master plan or blueprint of the cell.