One important job of the innate immune system is to detect when a foreign substance has entered the body. Recognition of a foreign substance typically results in inflammation and may recruit an adaptive immune response. Toll-Like Receptors (TLRs) are commonly discussed as detectors in the innate immune system but in the airway there are also epithelial cells that use bitter taste receptors to detect bacteria!
Solitary chemosensory cells (SCCs) are found in the nose and in the trachea. While it is unclear how similar these two populations of cells are they both have the same protein machinery that taste receptor cells use to detect bitter substances. Including members of the bitter taste receptor family, Tas2R. However, when these cells are stimulated it does not result in the sensation of bitter in your airways but rather pain. SCCs do not form synapses with nerves that conduct taste information but rather nerves that conduct pain information. Thus when stimulated by bacteria SCCs cause the sensation of pain and irritation in the airway.
Many gram-negative bacteria communicate their presence to each other using acyl-homoserine lactones (AHLs). AHLs concentration increases with the number of bacteria and at high concentrations ALHs can signal bacteria to become virulent. Lactones produced by plants are known to taste bitter and a recent paper has demonstrated that bacterial lactones can stimulate the bitter taste receptors on solitary chemosensory cells (Tizzano et al., 2010). This provides a mechanism by which the nervous system can detect a growing bacterial infection in the airway.
Activation of SCCs by ALHs results in stimulation of pain fibers along the respiratory tract. In the short term, stimulation of these pain fibers cause the sensation of irritation and produced protective respiratory reflexes. These protective respiratory reflexes, such as coughing and sneezing, promote clearing of the airway which may expel pathogenic bacteria. In the long term, stimulated respiratory pain fibers release pro-inflammatory chemicals such as substance P at the site of stimulation. This type of inflammation typically results in attracting dendritic cells and allows the recruitment of the adaptive immune system.
In light of these discoveries, perhaps we should start considering the bitter taste receptor family as pattern recognition receptors similar to TLRs. Just as some TLRs respond to certain pathogen-associated molecular patterns, bitter taste receptors respond to AHL which are produced by a variety of pathogenic bacteria. Additionally, stimulation of bitter taste receptors on SCCs and TLR both result in inflammation which recruits the adaptive immune system.
Bibliography
- Finger TE, Bottger B, Hansen A, Anderson KT, Alimohammadi H, Silver WL. 2003. Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc Natl Acad Sci U S A 100: 8981-8986.
- Tizzano M, Gulbransen BD, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill ME, Silver WL, Kinnamon SC, Finger TE. 2010. Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci U S A 107: 3210-3215.
- Tizzano M, Cristofoletti M, Sbarbati A, Finger TE. 2011. Expression of taste receptors in solitary chemosensory cells of rodent airways. BMC Pulm Med 11: 3.
One of the more solid posts. I loved how you not only described a cool receptor thet responds to bacteria by smell, using substance P, you have also shown how innate immunity and adaptive immunity interact via DC's. I thought it was interesting how SCC's act as if they were TLR's by recruiting DC's. The difference is that SCC's produce a macroscopic response by causing irritation and sneezing. I wonder if the SCC's have any method to attack a possible infection itself, or whether they have to recruit other immune cells to come help. I suppose cells like this wouldn't be so useful in the gut, as there are many beneficial bacteria that live in this environment. Anyway, great post.
ReplyDeleteI'm glad you enjoyed the post! My thesis project is on SCCs and I feel like they are an amazing biological adaptation that more people need to hear about. You actually brought up a few important points so I’ll address them below.
ReplyDelete1) The irritation that you feel when SCCs are stimulated isn't smell. The SCCs form synapses with pain fibers which are part of the somatosensory (touch) system. If you like spicy foods you are actually familiar with this, the "smell" of most spices is actually chemicals stimulating the somatosensory system. The proper term for this phenomenon is chemesthesis. A good rule of thumb is if a chemical causes a warming or cooling sensation its chemesthesis, not taste or smell.
It is actually pretty common for people to confuse taste, smell, chemesthesis and flavor. Those of us that study chemical senses spend a lot of time making sure that people understand the difference. If you are interested in the differences between the chemical senses here is a website that has good definitions for those terms: http://www.tastingscience.info/Explained/Terms.htm
2) Right now we don’t think that respiratory SCCs are doing anything other than being bacteria detectors but their stimulation may result in effects independent of irritation. For example, over half the tracheal SCCs don’t form synapses with any nerves. This might be an indication that they are signaling to the cells around them in addition to pain nerves. One idea that has been proposed in the literature is SCCs may release chemicals messengers that cause ciliated cells to beat faster which could dislodge growing bacteria.
3) You actually do have cells similar to SCCs in your gut. It is not as clear what their function is or if they are similar enough to the cells in your airway to also be called SCCs. They are useful because most the bacteria that make AHLs are dangerous, unlike the symbiotic bacteria in your gut. Additionally, lots of poisonous substances are bitter. One hypothesis is the SCC-like cells in the gut might cause vomiting or diarrhea to clear the gastrointestinal tract if they detect AHLs from virulent bacteria or potential poisons. Here is a citation to one of my favorite articles about the gut cells: Bezencon C, Coutre J, Damak S. 2007. Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chemical Senses 32: 41-49.
Hello,
ReplyDeleteThank you for the good writeup. Innate immune system is thought to constitute an evolutionarily older defense strategy, it is the response to infectious and sterile injury is modulated by neural circuits that control cytokine production...