Wild animals offer study of human immune system

The new work on wild immune systems casts diseases in humans in a new light

High in the Wallowa Mountains of northeastern Oregon, Raina K Plowright and other researchers blindfolded and hobbled a herd of bighorn sheep in a corral so blood samples could be taken and their noses and throats swabbed.

“There’s lots of places for pathogens to hide in the nasal cavity,” said Plowright, a wildlife scientist with the Centre for Infectious Disease Dynamics at Penn State who is based in Bozeman.

Peering into the nostrils of wild sheep is part of the nascent field of eco-immunology, which seeks both to understand the immune systems of wild animals and to use that knowledge to gain a better understanding of human immune systems. Until recently, this kind of knowledge has been gleaned almost exclusively by studying pampered, genetically similar lab animals, which don’t reflect a real-world scenario.

Eco-immunology works to understand how disease spreads in wildlife populations – the bighorn sheep are in trouble because of pneumonia that spread from domestic sheep – and how it can be worsened by human and environmental factors like climate change. Another major goal is to understand the pathways that deadly diseases can follow from wildlife to humans. In the past 30 years, more than 300 infectious diseases in humans originated in animals, including AIDS, Ebola, SARS, Lyme, hantavirus, West Nile virus and new strains of flu. (Diseases do not travel in just one direction. Humans are believed to have passed metapneumovirus to mountain gorillas in Africa.)

In her native Australia, Plowright was involved in pioneering disease research on the little red flying fox, an intelligent nectar-sipping bat with winsome puppy-dog eyes.
After the 1994 emergence of a deadly virus called Hendra in humans and horses in northeastern Australia, biologists found that it came from flying foxes. That led to widespread calls to cull bats or frighten them away from places where people lived.

In 2008, however, Plowright made a crucial discovery. Stress appears to weaken the bats’ immune system, and that is when they are likely to shed the most virus.

“It’s the idea that if you get rundown you get sick,” she said. “So trying to kill or move bats could make things worse by stressing them” and causing them to excrete more of the virus in their waste. The finding has quieted calls for large-scale bat removal, and Australia has committed several million dollars to a three-year project to understand viral ecology in bats.

The interconnections between human and animal diseases have led to new efforts to understand these mechanisms, including the One Health Initiative, a program that unites medical and veterinary scientists in interdisciplinary approaches to disease and environmental degradation.

Wild-animal immunity also provides a near-pristine system to study. “The wild is a null system, a system without interference,” said Peter J Hudson, a biologist at Penn State and a founder of the infectious disease center there.

“Research on wild systems,” he continued, “will help us answer the question of ‘Should we interfere, and how does interference affect the ecology and evolution of these bugs? Will the application of vaccines and antibiotics create more health problems?”’

Some researchers believe, for example, that the rise in autoimmune disorders may be caused by a lack of stimulation of human immune systems by certain microbes. And while that idea would be hard to evaluate in human studies because our immune systems have been altered for decades with antibiotics and more sterile environments, Hudson said that “wildlife systems can give us that insight.”

Much about the diseases that originate in wildlife is a mystery. In the case of bat viruses, experts believe they evolved for millions of years in intact bat ecosystems, with the animals passing it to one another over and over, causing low-grade infections and building their immune defences.

Jonathan H Epstein, a veterinarian and a disease ecologist with EcoHealth Alliance, a nonprofit group in New York, has used experimental infections to understand Nipah virus, which is closely related to Hendra.
“These bats don’t even break a sweat when they are raging with Nipah virus,” he said. “So they are really good at spreading it. But a naive immune system” – like those of humans and horses with respect to Hendra – “goes crazy.”
The new work on wild immune systems casts disease in a new light: as an environmental issue. One ecological driver of bat virus transmission is development in the flying foxes’ natural habitat. Instead of living in a wild forest, the bats swoop into the cities and suburbs that replaced it, feeding on nectar in gardens and trees and then passing viruses along to horses and humans.

Common thread

A common thread, disease ecologists say, is that clearing or altering a forest can be akin to opening a Pandora’s box. Keeping nature intact, or developing it in sustainable ways, protects against disease.

“If you conserve an ecosystem you have a jolly good chance of conserving human health as well,” said Simon Anthony, a molecular virologist with EcoHealth who is studying the ecology of Nipah and other viruses.

Richard S Ostfeld, a disease ecologist at the Cary Institute for Ecosystem Studies in Millbrook, N.Y., has been studying the causes of Lyme disease, which causes fatigue, achy joints, fever and chills and has been linked to neurological and heart disease.

White-footed mice are a reservoir for the bacteria that creates Lyme, and Ostfeld says one reason they are so successful at it is that they reproduce very rapidly when the woods are developed and their predators disappear.

“The fast dudes like mice are incredibly resilient in the face of human disturbance,” he said. And because they live only six months, they may put their energy into breeding at the expense of immune defence and so magnify the prevalence of Lyme.
Diseases might even be spread by things that are otherwise good for the environment. The notion of connecting fragmented habitats so wildlife have access to critical habitat has been gaining ground. But disease ecologists say it may also spread disease.

Bighorn sheep, for example, are moved around the West by wildlife agencies to build populations – but with little thought to pneumonia, Plowright said.

“When we alter the environment abruptly,” Plowright said, “we radically change the balance between diseases and the immune system, which can affect the entire web of life, including humans. We are just beginning to understand this.”