Bacteria that cause Lyme disease may hide out in the lymph nodes, triggering an immune response that is significant but not powerful enough to fend off the infection, UC Davis researchers found in a new study.
The study, published online in the journal Public Library of Science Biology at http://tinyurl.com/3vs8pm9, used mice to discover why some people experience repeated infections of Lyme disease.
Lyme disease, which a major tick-borne disease in the United States, is caused by Borrelia burgdorferi, corkscrew-shaped bacteria also known as spirochetes. The disease is transmitted to humans and animals through bites from infected deer ticks. The disease occurs mainly in the Northeastern and Great Lakes states, and is present to a lesser extent in Northern California.
Symptoms of Lyme disease vary and may include fever, headache, fatigue and a skin rash. If the infection is not treated, it can spread to the joints, heart and nervous system.
Usually, Lyme disease can be successfully treated with about four weeks of antibiotics; treatment is most successful during the early stages of infection.
“Our findings suggest for the first time that Borrelia burgdorferi … have developed a novel strategy for subverting the immune response of the animals they infect,” said Professor Nicole Baumgarth, an authority on immune responses at the UCD Center for Comparative Medicine.
“At first it seems counter-intuitive that an infectious organism would choose to migrate to the lymph nodes where it would automatically trigger an immune response in the host animal,” Baumgarth said. “But B. burgdorferi have apparently struck an intricate balance that allows the bacteria to both provoke and elude the animal’s immune response.”
Swollen lymph nodes, or lymphadenopathy, is one of the hallmarks of Lyme disease, although it has been unclear why this occurs or how it affects the course of the disease. The UCD research team set out to explore in mice the mechanisms that cause the enlarged lymph nodes and to determine the nature of the resulting immune response.
They found that when mice were infected with B. burgdorferi, the live spirochetes accumulated in the animals’ lymph nodes. The lymph nodes responded with a strong, rapid accumulation of B cells, white blood cells that produce antibodies to fight infections.
Also, the presence of B. burgdorferi caused the destruction of the distinct architecture of the lymph node that usually helps it to function normally.
While B cells accumulated in large numbers and made some specific antibodies against B. burgdorferi, they did not form “germinal centers,” structures that are needed for the generation of highly functional and long-lived antibody responses.
“Overall, these findings suggest that B. burgdorferi hinder the immune system from generating a response that is fully functional and that can persist and protect after repeat infections,” Baumgarth said. “Thus, the study might explain why people living in endemic areas can be repeatedly infected with these disease-causing spirochetes.”
In addition to Baumgarth, members of the research team include Stephen Barthold, director of the Center for Comparative Medicine; Emir Hodzic, director of the Real-Time PCR Research and Diagnostics Core Facility; staff scientist Sunlian Feng; graduate student Christine Hastey; and Stefan Tunev, formerly of the Center for Comparative Medicine and now at Medtronic Inc.
Funding for the study was provided by the National Institutes of Health.