The incurable infection caused by cytomegalovirus (CMV) – a species in the same widespread, human-targeting family as herpes, chickenpox, and Epstein-Barr – has long been presumed to negatively impact our immune systems in old age. After all, once present in the body – and more than half of adults have contracted it by age 40 – CMV is with us for the rest of our lives; presenting a constant target for our white blood cells to tire themselves against. And because our pathogenic defenses naturally decline over time anyway, it is logical to presume that having CMV will make us more susceptible to infections in later years.
Yet new research led by the University of Arizona now implies the opposite. In a study published in Proceedings of the National Academy of Sciences, a team of immunobiologists under Megan Smithey and Dr Janko Nikolich-Žugich describe how CMV-positive elderly mice actually have a more vigorous immune response against bacterial invaders.
Hoping to evaluate how CMV hinders lifelong immunity, Smithey, Nikolich-Žugich, and colleagues began by infecting mice with CMV at age 20 weeks, then waited until the animals were 20-months-old (middle aged for the species) to infect them with Listeria monocytogenes – a highly virulent and potentially deadly foodborne pathogen.
Expecting to see the CMV mice’s T cells struggling to identify and attack the Listeria, the team was shocked to find that CMV-positive animals not only showed a vigorous immune response, but they produced a diverse set of white blood cells capable of recognizing a broader variety of Listeria proteins than the cells of non-CMV control mice.
“We assumed it would make mice more vulnerable to other infections because it was using up resources and keeping the immune system busy,” Smithey said in a statement. “We were completely surprised; we expected these mice to be worse off. But they had a more robust, effective response to the infection.”
Unsure of where this reaction came from, the authors subsequently analyzed all the existing T cell types – called a repertoire – within CMV-positive old mice and CMV-negative adult and old mice. The results proved that individuals of all ages and viral status harbor diverse cell lineages; yet for unknown reasons, old mice with CMV appear to be far superior to other old mice at recruiting this wealth of T cells when a new, unrelated threat arises – a process called adaptive heterologous immunity.
“Diversity is good,” Dr Nikolich-Žugich explained. “Different types of T-cells respond to different types of infections; the more diverse T-cells you have, the more likely you’ll be able to fight off infections.”
“This shows that the ability to generate a good immune response exists in old age — and CMV, or the body’s response to CMV, can help harness that ability,” Smithey concluded.
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