That 2010 study, Love told me, “sort of blew my mind,” because it didn’t follow the typical trajectory of the immune system reacting to an ongoing assault. Instead, the cells were internalizing visual cues and buttressing themselves preemptively—raising shields against an attack that hadn’t yet happened, and perhaps never would. It was what you might call bystander immunity, and it was totally bizarre.
Love decided to try her own version in domestic canaries, among the many bird species susceptible to a pathogen called Mycoplasma gallisepticum. She infected 10 canaries with Mycoplasma, then placed them in sight of microbe-free birds. In parallel, she had two other cadres of healthy canaries scope each other out, as a symptomless point of comparison.
Throughout the 24-day experiment, the uninfected canaries acted as most songbirds do, feeding, chirping, and bopping cheerily around their cages. But about a week in, the birds dosed with Mycoplasma became mopey and lethargic, and developed a nasty form of pink eye. “I could approach the cage and just pick them up,” Love told me. (Some Mycoplasma species can cause disease in humans; this one doesn’t.)
The birds watching their beleaguered peers never got infected themselves. But when Love and her colleagues examined the canaries’ blood, they found that some of the birds’ immune responses had swelled in near lockstep with the sick birds’ symptoms. Cells called heterophils—inflammation-promoting foot soldiers that fight on the front lines of many avian infections—had flooded the bloodstream, similar to how they would in the presence of Mycoplasma, Love said. The birds’ blood was also rife with so-called complement molecules, which can shred bacterial cells, or flag them for other types of destruction.
The uptick was temporary. As the symptoms of the sickened birds abated, their observers’ immune cells quieted down as well. Love told me she suspects that these little flare-ups might have primed the watchful birds for a possible tussle with the pathogen—perhaps cloaking them in a light layer of armor, akin to a very crude and very ephemeral vaccine.
To confirm that idea, Love would have needed to expose the onlooker birds to Mycoplasma while their immune systems were still raring to go, an experiment she is working on now. Without those data, “it’s hard to know what this means,” Jesyka Meléndez Rosa, an immunologist at Humboldt State University who wasn’t involved in the study, told me.
The immunological surge did seem driven by the disease cues that the other birds emitted, because samples taken from the canaries who’d peeped on only healthy birds stayed comparatively inert. But what the researchers found could have just been a blip—noticeable, yet not strong enough to alter the trajectory of a subsequent infection. A bystander immune response could even be a net negative for the witness, wasting precious bodily resources or unnecessarily damaging healthy tissues. Heterophils and complement molecules also comprise just a small subset of the immune system’s arsenal, much more of which would be marshaled into quelling a Mycoplasma invasion. Letícia Soares, a disease ecologist at Western University who wasn’t involved in the study, told me she wished she’d been able to see how well the observer birds’ immune responses simulate what happens in infected birds who eventually recover.