Cells of the human immune system recognize the bacterium Streptococcus pyogenes differently from what has been assumed until now. Within a research project financed by the Austrian Science Fund (FWF) microbiologists from the University of Vienna now published surprising results of the first study, which investigates the details of the immune response to Streptococcus.
The bacterium Streptococcus pyogenes causes numerous disorders in humans such as scarlet fever, tonsilitis, wound infections, septic shock or, as a long-term consequence, rheumatic fever or kidney diseases. Severe infections of Streptococci have mostly one thing in common: an over-reaction of the immune system, which is difficult to treat or even results in life-danger for the patient. After the pathogen enters the body, the scavenger cells (macrophages) of the congenital immune system are activated. As a first step a receptor molecule of the macrophage needs to recognise the bacterium to get the immune reaction started.
Until now, it has been assumed that receptor molecules of the Toll-like receptor group (TLRs) are responsible for the recognition of Streptococci and pass a signal to the central signalling molecule MyD88 to turn the immune response on. The research groups of Pavel Kovarik and Emmanuelle Charpentier at the Max F. Perutz Laboratories at the Campus Vienna Biocenter in Vienna now found out, that none of the known TLR-receptor molecules has something to do with the first step of Streptococcus recognition, though the already known MyD88 molecule is used in the second step for further signalling. The results of the first study, which investigates the cellular recognition mechanisms of the immune system’s activation were now published in the Journal of Biological Chemistry.
"It is a big surprise that not the TLR2 receptor is responsible for the recognition of Streptococci infections“, says Pavel Kovarik, immunobiologist of the University of Vienna. “And none of the other molecules of this receptor group is taking part in the mechanism, though the well-known MyD88 is used for the second step of signal transduction. We now begin the exciting search for a totally unknown receptor“, outlines Kovarik the plans for his next research project.
Until now it is unexplained why infections with Streptococci result in particularly severe disorders and complications of therapy. The researchers presume that this unknown receptor molecule may be the missing link in the understanding of the human immune response to this bacteria strain.
Pavel Kovarik’s search for the new receptor will be accompanied by his colleague Sylvia Knapp, researcher at the Center of Molecular Medicine (CeMM) of the Austrian Academy of Sciences and medical specialist of infectiology at the general hospital (AKH) in Vienna. Also the biotechnology company Intercell AG is interested to participate in the project. The goal of the basic scientist Kovarik and the clinician Knapp: to identify the unknown molecule participating in the mechanism of Streptococcus-recognition and subsequently find a substance to regulate the over-reaction of human immune cells.
Original publication: Gratz N, Siller M, Schaljo B, Pirzada ZA, Gattermeier I, Vojtek I, Kirschning CJ, Wagner H, Akira S, Charpentier E, Kovarik P. Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9. J Biol Chem. 2008 Jul 18;283(29):19879-19887.
The Max F. Perutz Laboratories are a joint-venture of the University of Vienna and the Medical University, founded 2005. This inter-university collaboration is a new and innovative approach to strengthen research and education at both universities. The 60 research groups at the institute in the Bohr-Gasse work in the area of molecular cell biology. Since 2007the Scientific Director of the institute is Graham Warren, a biochemist and former Yale-professor.