ICAAC Highlights
Mice under stress reactivate with TB
An animal model showing how stress can reactivate latent tuberculosis in mice may help explain the shift from latency to reactivation in humans, says the scientist who developed it.
When mice with a steady-state TB infection were stressed by being placed in uncomfortably close quarters, the animals’ bacterial counts rose markedly, says Bruce Zwilling, PhD, professor of microbiology at Ohio State University in Columbus. Next, after the mice were removed from the stressful environment, they were able to re-exert immunologic control over their disease, he adds.
In addition, Zwilling identified a shift in the kind of cytokines the mice were producing, from TH1 to TH2, which corresponded to the rise and fall in stress, as well as the rise and fall of bacterial loads. The two findings offer a clear analogy for what goes on in humans latently infected with TB who experience stress, he concludes.
"Conventional wisdom has always included the notion that stress is one risk factor for reactivation of TB, but it’s been difficult to study that perception," he explains. "For one thing, there are too many confounding factors in peoples’ lifestyles [to be able pinpoint a particular stress]."
For another, it’s not possible for a study to isolate a period in humans where they are shifting from latency to reactivation because "people either have latent disease, or they have active disease," he says. "And they don’t go to the doctor unless they have active disease."
In his study, Zwilling put mice into a "restraint model" (consisting of a 50 mm centrifuge tube) every night for two five-night sessions. Inside the tube, the mice could not turn around or back up. The animals were released from the tube during the daytime and weekends. During the restraint sessions, the animals’ glucocorticoid levels rose and stayed elevated, returning to normal levels after the stress periods had ended.
Before the restraint sessions were initiated, Zwilling already had induced a steady-state TB infection in the animals. Colony counts in the animals showed that after four weeks of stress, the number of microorganisms began to rise. Even tually, the mice re-exerted immunologic control, and their colony counts began to subside until a steady-state infection was re-achieved.
To Zwilling, latently infected human beings placed under stress may react the same. "If you look at the literature from the pre-antibiotic era, people would get sick and then they’d get well again," says Zwilling. "They’d take rest cures.’ Immuno compromise occurs during the stressful periods."
The link between stress and the immune system has been implicated in other illnesses as well. People with a common cold virus, or those who undergo a reactivation of a herpes virus, likewise self-report having been under high levels of stress.
Zwilling also documented shifts in the stressed animals’ lymphocyte populations, which changed from TH1, which helps control TB, to TH2, which "permits" TB. The shift from "controlling" to "permissive" cytokines took place in both CD4 and CD8 cells, he notes.
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