IL-1 family cytokines as the canonical DAMPs of the immune system

Hello, I'm Seamus Martin from Trinity College Dublin in Ireland. Today, I'm going to be talking about members of the IL-1 cytokine family and their role as canonical DAMPs of the immune system. DAMPs, as I'm going to be talking about a lot today, are molecules that are essentially damage-associated molecular patterns. As we shall see, these are important molecules that drive inflammation in the context of necrosis or tissue damage.

As you know, inflammation is initiated by two main drivers, either strangers in the form of infectious agents, such as bacteria or viruses and the concept of PAMPs was introduced by Charles Janeway about 30 years ago when he suggested that infectious agents all contain the so-called pathogen-associate molecular patterns. These are molecules that are effectively unique to microbial agents that are not present normally in the body. These PAMPs are essentially interpreted by the body, by the immune system as being indicative of infection or non-self. PAMPs are introduced into the body by infectious agents, and then they trigger or are sensed by pattern recognition receptors, receptors that are essentially trained to recognize PAMPs. In the other scenario, you've got molecules that are indicative of danger. As we shall see, Polly Matzinger realized that effectively inflammation can be initiated by things other than strangers, by things other than infectious agents. By realizing that in the context of sterile immunity, where you don't have an infectious agent in the body, but instead, you have tissue damage or tissue stress caused by either physical injury, by toxins, noxious agents, or things that effectively just perturb normal homeostasis in cells. You have a situation where self-molecules, which she dubbed danger signals at the time, are now more commonly called DAMPs, or damage-associated molecular patterns. These self-molecules are released from cells or released from one particular cellular compartment into another, such as released from mitochondria into the cytosol, and these DAMPs can also trigger inflammation. As we shall see, they trigger inflammation by being sensed by a different type of pattern recognition receptor, and they are also able to drive inflammation. Inflammation can be initiated by either PAMPs associated with strangers or by DAMPs associated with danger in the form of tissue damage or tissue stress. In both cases, either PAMPs or DAMPs can drive inflammation.