Ashley Yeager in The Scientist:
“Anytime we take Tylenol because we have the flu and we feel terrible, that’s actually you playing with tolerance,” says Stanford University microbiologist David Schneider, Ayres’s former advisor. By quieting the immune reaction that is making you feel sick, “you’re making yourself feel better, even though you might not be affecting how much of a pathogen is in your body.” As they come to appreciate that disease tolerance exists in animals, including humans, researchers want to tap into its mechanisms—analogous to the way they are tapping into the immune system to develop disease-fighting immunotherapies. Specific kinds of supplements, as Ayres has shown in mice, may be one solution. And bacteria that live in the body as part of its microbiome have been shown to help mice tolerate malaria, Salmonella, and pneumonia infections. “During infection, we all appreciate that there are these immune defenses that largely are designed to get rid of an invading pathogen, and that’s been thought to be the only or main way that we deal with infections,” says Ruslan Medzhitov, an immunologist at Yale School of Medicine. “What’s being appreciated more recently . . . is that there is also this other mechanism, so-called tolerance to infection, where instead of trying to get rid of a pathogen we change something about the body, about the physiology, and that lets us tolerate the presence of a pathogen.”
Until about a decade ago, researchers had largely overlooked the idea of disease tolerance in animals. But the physiological strategy didn’t go unnoticed among plant biologists. In research dating to the late 1800s, for example, scientists described how one variety of wheat crop infected with a fungus called leaf rust fared better and produced more grain than other infected wheat crops.2 Follow-up studies spanning the 20th century and into the 21st suggested that plants have internal ways to tolerate infections in addition to defending against them with immunity. These findings led researchers to wonder if a similar sort of tolerance exists in animals.
Researchers reported the first hints of disease tolerance in humans in 2006, when they found that people who have a type of alpha thalassemia, a blood disorder that typically reduces hemoglobin production, are somehow protected against the severe iron deficiency associated with a malarial infection. In a study published the following year, disease ecologist Andrew Read, then at the University of Edinburgh, and his former postdoc Lars Råberg found that certain strains of mice had genetic variations that boosted their tolerance to the malaria parasite Plasmodium chabaudi. Those mice had improved health, the researchers noted, but comparable numbers of P. chabaudi cells in their bodies to those in mice that weren’t as tolerant to the infection.3