Side Effect of Rheuma Treatment: Why Life-Threatening Infections Can Occur
Dendritic cells are cells of the immune system. They owe their names to the typical tree-like branches (from the Greek word dendron for tree)
Tumor necrosis factor alpha (TNFa) blockers can be used very successfully in the treatment of rheumatoid arthritis. However, the medication increases the risk of getting a serious infection, such as with listeria bacteria. Scientists of the National Genome research network (NGFN) have just found out how this dangerous side effect occurs. They discovered that TNFa is essential for the formation of granuloma and thus of the body’s own immune response to an infection with listeria pathogens.
With the encapsulation of disease pathogens by forming abscesses and granuloma, the innate immune defense protects the body.
Granuloma are nodule-like new tissue formations which mainly consist of macrophages and dendritic cells of the immune system. The function of macrophages in fighting bacteria is already known: They encapsulate the bacteria inside their cells and thus isolate the disease pathogens from healthy tissue.
Listeria bacteria (blue) penetrate the intestinal cell (beige) and infest the neighboring cell. (courtesy of GBF, Professor Heinz)
"After an infection with listeria pathogens, the dendritic cells produce the protein indolamine 2,3 dioxygenase (IDO)," explains the leader of the study, Professor Joachim L. Schultze of the University of Cologne.
IDO acts like tiny scissors that catabolize the protein building block tryptophan.
The increased degradation of tryptophan in turn inhibits the growth of bacteria, which require tryptophan as nutrient or for which – as in the case of listeria – its degradation products are toxic. The tryptophan degradation products also have another function: They inhibit the body’s own T cells.
This inhibition of T cells is very important, because T cells recognize and destroy infected cells. Without an inhibition by the dendritic cells, the T cells would also destroy the granuloma, release the encapsulated pathogens in the body and thus make the infection worse.
The NGFN researchers showed that the dendritic cells increasingly form the molecular IDO scissors only if the messenger substanceTNFa is also present. If specific blockers suppress TNFa, an infection with listeria pathogens can take on life-threatening proportions:
Because the T cells are not inhibited, they destroy the protective granuloma, and the released disease pathogens flood the body. TNFa blockers are used e.g. in the therapy of rheumatoid arthritis, because TNFa here contributes to the typical chronic joint inflammation which is a key characteristic of this disease. Accompanying the therapy with TNF-ainhibitors, the researchers additionally recommend administering antibiotics, if necessary, to prevent these disease pathogens from spreading in the body.
