Scientists reveal the first close-up of a bat’s immune response to a live infection

Scientists reveal the first close-up of a bat's immune response to a live infection

Eonycteris spelaea as seen in a captive colony. Credit: Duke-NUS Medical School

For the first time in the world, researchers at Duke-NUS Medical School and colleagues in Singapore have sequenced the response to viral infection in colony-bred cave nectar bats (Eonycteris spelaea) at single-cell resolution. Published in the magazine Immunitythe findings contribute to insights into bat immunity that could be harnessed to protect human health.

Bats harbor many types of viruses. Even when infected with viruses that are fatal to humans, they show no obvious signs or symptoms of the disease.

“It is our hope that by understanding how bats’ immune responses protect them from infection, we may find clues that will help humans better fight viral infections,” explained Dr. Akshamal Gamage, a research fellow with Duke-NUS’ Emerging Infectious Diseases (EID) program and co-first author of the study.

“And knowing how to better fight viral infections can contribute to the development of treatments that will help us be more bat-like – by getting sick less and aging better,” added Mr. Wharton Chan, MD-Ph.D. candidate at Duke-NUS who is also the study’s co-first author.

In this study, the researchers investigated the immune response of bats to Malacca virus, a double-stranded RNA virus that uses bats as a natural reservoir. This virus also causes mild respiratory disease in humans.

The team used single-cell transcriptome sequencing to study the lung’s immune response to infection at the cellular level, identifying the different types of immune cells in bats – some of which differ from those in other mammals, including humans – and revealing what they do in response to such viral infections.

They found that a type of white blood cell called neutrophils showed very high expression of a gene called IDO1, which is known to play a role in mediating immune suppression in humans. The researchers believe that the expression of IDO1 in cave nectar bats may play an important role in limiting inflammation following infection.

Dr. Feng Zhu, a research associate in the EID program and co-first author of the study, said: “We also found marked antiviral gene markers in white blood cells called monocytes and alveolar macrophages, which – in a sense – ingest viral particles and then teach T cells how to to know the virus. This observation is interesting as it shows that bats clearly activate an immune response following infection despite showing little outward signs or pathology.”

The team also identified an unusual diversity and abundance of T cells and natural killer cells — named for their ability to kill tumor cells and virus-infected cells — in the cave bat, which are commonly activated in response to infection.

“This is the first study to report the bat immune response to in vivo infection at the single-cell transcriptome level,” said Professor Linfa Wang, senior author of the study from the EID Program.

“We believe our work is a key guide to inform further research on uncovering the amazing biology of bats. Going forward, in addition to research on viral disease resistance, we also hope to uncover evidence of longevity from bats as long-lived mammals and also learn how these nectar-eating bats can live on a high sugar diet in nectar without developing diabetes.”

More information:
Akshamal M. Gamage et al., Single-cell transcriptomic analysis of the in vivo response to virus infection in the cave nectar bat Eonycteris spelaea, Immunity (2022). DOI: 10.1016/j.immuni.2022.10.008

Provided by Duke-NUS Medical School

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