Bats’ immune systems evolved to slow down the response to disease-causing inflammation

Edit Hook

Bats can safely harbor many viruses that kill other animals without getting sick. Their superpower? An immune system that has evolved a way not to mount a defense against some infections.

An animal’s immune system recognizes potentially harmful foreign matter like viruses and bacteria when they enter the body. It also clears the remnants of cells that die and break down in the normal course of living. Proteins called inflammasomes that sense alien invaders are critical components of the immune system. These trigger the production of other immune cells that seek and destroy intruders. 

But the immune response is not without risk to its owner. When immune cells flood in to fight infection, they naturally cause inflammation—swelling, heat, redness and pain. Normally, the cells get rid of the harmful matter quickly and the inflammation subsides. But sometimes, viruses can rev up an animal’s immune system too much. The inflammation becomes too intense or lasts too long. Then it can damage surrounding tissue and cause disease. 

But scientists don’t see viruses triggering the same response in bats. Recent studies have shown that these mammals have a slight variation in their inflammasomes. As a result, they do not readily trigger floods of immune cells to fight viruses. And so bats can tolerate large amounts of many different kinds of viruses without suffering inflammatory diseases like rabies, Ebola, severe acute respiratory syndrome (SARS) and COVID-19. That’s important because they eat loads of virus-carrying insects like mosquitoes. But it also makes bats a reservoir for diseases that can be lethal to people.

Some scientists think bats may have developed this trait because, unlike other mammals, they fly. It’s a behavior that takes a lot of energy and increases wear and tear on cells that release more broken-down cellular bits. The immune system must clean this mess up. If bats had not evolved the ability to dampen their immune response, flying would cause constant inflammation in their bodies. 

The altered inflammasome may also contribute to bats living so long—up to 40 years. As animals age, cells in their bodies break down more often, triggering inflammation and diseases. Any process that reduces inflammation gives those that have it better chances of living longer.

By understanding how bats tolerate viruses, scientists can find ways to prevent them from transmitting deadly diseases like COVID-19 to people. And by learning how bats’ immune systems dampen inflammation responses, they can explore therapies and drugs that could do the same in people to reduce the impacts of other diseases caused by inflammation and aging. These include heart and circulatory system diseases, arthritis, allergies and asthma.

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Bats, as the only flying mammals, have ‘emerged’ in both the scientific and general public arenas due to their ability to asymptomatically host a large number of high-profile viruses. … Bats also have an extraordinarily long lifespan relative to their body size, despite their elevated metabolic rates. …. Here, we report a mechanism by which bats dampen host inflammation in response to both ‘sterile’ danger signals and infections with three different zoonotic RNA viruses. … with implications for longevity and asymptomatic viral reservoir status.” (Ahn et al. 2019:789)

Journal article
Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir hostNature MicrobiologyFebruary 25, 2019
Matae Ahn, Danielle E. Anderson, Qian Zhang, Chee Wah Tan, Beng Lee Lim, Katarina Luko, Ming Wen, Wan Ni Chia, Shailendra Mani, Loo Chien Wang, Justin Han Jia Ng, Radoslaw M. Sobota, Charles-Antoine Dutertre, Florent Ginhoux, Zheng-Li Shi, Aaron T. Irving, Lin-Fa Wang

Journal article
Dampened STING-Dependent Interferon Activation in BatsCell Host & MicrobeFebruary 22, 2018
Jiazheng Xie, Yang Li, Geraldine Goh, Yan Zhu, Jie Cui, Lin-Fa Want, Zheng-Li Shi, Peng Zhou

Web page
Could an NLRP3 inhibitor be the one drug to conquer common diseases?c&en (chemical & engineering news)February 17, 2020
Ryan Cross

Web page
Why Bats Make Such Good Viral HostsThe ScientistMay 31, 2018
Katarina Zimmer

Web page
The bat-virus détenteKnowable MagazineJune 19, 2020
Rachel Ehrenberg

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