It’s flu season in the northern hemisphere and with it comes fever, aches, coughing, and general fatigue. The flu comes and goes within a couple of weeks for most people, however for some of the population a simple flu can progress into serious disease and even hospitalization. As many as 8000 people may be hospitalized with a severe form of the flu in Canada in any given year. Currently the flu is treated with bed rest and plenty of fluids. In severe instances, anti-viral medication can be used but at best these drugs may only reduce the length of the infection by one day. In order to develop better treatments for this yearly disease we need to better understand how the immune system of the lung responds to viruses like influenza. In your lung reside a type of cell called alveolar macrophages whose job it is to eat up foreign matter you inhale daily. This can include viruses, bacteria, fungi, dust, pollen, or other pollutants. These macrophages are the front line defense system of your lung. Since these cells are key to orchestrating the immune response to foreign invaders in the lungs, a group of researchers from Texas took a closer look at how they respond when they encounter the flu virus.
The researchers specifically focused on a protein called TRIM29 (tripartite interaction motif 29) whose job it is to target proteins for destruction. Sometimes these proteins may be defective or, in the case of TRIM29, the proteins may be broken down to turn on other key proteins. Pretend that your energy bill is too high so you get TRIM29 to go around your house and cut all the cords supplying power to your electronics. Now that no electronics work your energy bill goes way down but you also can’t use any of the electronics. In this way TRIM29 prevents energy use by breaking the things that use energy. The researchers took mice who lacked TRIM29 (they deleted it from their DNA) and infected them with the flu virus (H1N1). They found that mice who had no TRIM29 were able to survive the infection while mice who still had TRIM29 could not (died within 9 days). Additionally, mice without TRIM29 were able to get rid of the infection within 2-4 days. This increased resistance to the infection was due to the release of interferons from the macrophages. Interferons act like danger signals or SOS’s for the body and it has been shown that people who can’t make enough interferons suffer from more severe flu. How does TRIM29 manage to do this? TRIM29 breaks down a protein that triggers inflammation in the lungs. This protein acts like the power cord for inflammation, cut it and you have no inflammation. Without inflammation your body cannot fight off the infection. When you get rid of TRIM29 inflammation is allowed to occur and the mice were able to then make interferons and fight of the virus. However, when these same mice were infected with bacteria, the mice died of sepsis (over loaded inflammation). This seems to be due to an inability of the immune system to turn off.
The story is complicated and it seems that there are two different responses depending on whether the mice were infected with a virus or bacteria. In the case of a bacterial infection, TRIM29 is beneficial in slowing down or stopping the inflammation from going overboard. In a viral infection TRIM29 is detrimental because it stops the macrophages from making enough SOS signals. We won’t know for sometime if we can target this protein to help clear of problematic influenza infections in people. We also don’t know if this same pathway works for other viral infections. The result also holds promise in helping us understand sepsis and what may trigger our immune system to go into overdrive.
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