Among other amazing features, our bodies come equipped with an innate immune response system. Somebody sneezes in our presence; and if were lucky, our immune system foot soldiers will recognize the unwelcome bug and zap it. If they dont recognize the invader, the innate system will trigger an inflammatory response in an attempt to wall off the intruder and stop its spread through an inflammatory response which is initiated by Toll-like receptors (TLRs).
These TLRs form an ancient family of proteins that mediate innate immunity in organisms from horseshoe crabs to humans. When they fail to work, they leave the body open to infection. Working too hard, they can induce disorders marked by chronic, harmful inflammation, e.g., autoimmune diseases.
Discovery of TLRs has brought excitement to immunologists as they suddenly see possibilities not understood before. Study of these receptors and of the molecular events that unfold after they encounter a pathogen is already beginning to uncover targets for pharmaceuticals that may enhance the body protective activity, bolster vaccines, and treat a range of devastating and potentially deadly disorders.
The innate immune response was essentially ignored as researchers embraced the adaptive response, so-called because over the course of an infection, it adjusts to handle the particular microorganism responsible for the disease. Adaptive immunity also endows the immune system with memory, thus giving it the ability to remember past infections and allowing vaccines to protect us from diseases caused by viruses or bacteria.
On the other hand, the adaptive system does not work in the absence of the innate response. The innate system produces certain signaling proteins called cytokines that not only induce inflammation but also activate the B and T cells that are needed for the adaptive response. Now scientists know that the TLRs identify the invading viruses or bacteria and sound the alarm to mobilize the troops and prepare the array of defenses needed to fully combat the attack. TLRs unleash both the innate and adaptive systems.
Some studies are pointing to roles for TLRs in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Here TLRs might respond to products from damaged cells, propagating an inappropriate inflammatory response and promoting a misguided reaction by the adaptive immune system. In lupus, for example, TLR9 has been found to react to the body own DNA.
TLRs are like the volume knob on a stereo, balancing adaptive immunity and inflammation. Researchers and pharmaceutical companies are now looking for ways to tweak these controls so that they can curtail inflammation without disabling immunity. Given that TLRs were unheard of seven years ago, investigators have made enormous progress in understanding the central role these proteins play in the body first line of defense. As researcher and professor Dr. Luke A. J. ONeill, of Dublin, Ireland, states, "Innate immunity, long shrouded in oblivion, has suddenly become the belle of the ball."
