IFN-a and IFN-b in antimicrobial immunity

Viral infection requires an immediate response of our immune system to inhibit pathogen replication and spread between cells and tissues. The rapid production of type I interferons, especially interferon-alpha (IFN-a) and interferon-beta (IFN-b) curtails viral growth by inducing cells to progress into an antiviral state. Type I IFN also help to contain bacterial infections, and they guide immune cells to infected tissues. In humans and animals, the lack of type I IFN-mediated protection causes severe viral illnesses. On the other hand, overshooting type I IFN activity can drive harmful inflammation and autoimmune diseases. IFN-a and IFN-b bind to the same cell surface receptor, and both have the ability to establish the antiviral state. Even after decades of research, it is still unknown whether and to which extent IFN-a and IFN-b can substitute for one another or have distinct, non-replaceable roles in body homeostasis and during infection. Our project directly addresses this knowledge gap by making use of a unique set of mouse models in which we can turn off IFN-b alone, the entire group of IFN-a genes, or both together. This side-by-side design enables us to determine how the immune system and other target cells and tissues behave when either one of the signals is missing or both are missing. Using advanced but well-established methods, we will map which cells produce each IFN in normal conditions and during infection, focussing on the spleen and the intestine. We will pinpoint which cells respond to IFN-a, IFN-b, or both, and track how these signals affect pathogen load and organ integrity over time. We will thus define specific requirements for either IFN-a or IFN-b and also look for interactive effects, such as cases where the two signals amplify each other or compensate when one is missing. By revealing the non-overlapping roles of IFN-a and IFN-b, our study will fill a major gap in understanding the bodys frontline alarm system. These insights can guide more precise use of IFN-based therapies and inform the design of new treatments and prevention strategies across a wide range of infectious and inflammatory diseases.

No additional funding sources recorded.