The presence of a certain molecule allows the immune system
to effectively police tuberculosis (TB) of the lungs and prevent it
from turning into an active and deadly infection, according to a
new study led by researchers at Children’s Hospital of Pittsburgh of
UPMC and the University of Pittsburgh School of Medicine. Their
findings appear in the Journal of Clinical Investigation.
More than 2 billion people —one-third of
the world’s population— are infected with
mycobacterium tuberculosis, the bacterium
that causes TB, says senior author
A. Khader, PhD
(left), allergist/immunologist
at Children's Hospital and assistant professor
of Pediatrics, University of Pittsburgh School
of Medicine. The infection is challenging to treat partly because
the bacillus is able to enter cells and linger for years without
causing symptoms, known as latent TB. Then, typically when the
immune system becomes impaired due to other reasons such as
age or HIV, the infection becomes active and causes the cough,
night sweats, fever, and weight loss that characterize the disease.
“A hallmark of TB that we see on chest X-rays is the
granuloma, a collection of immune cells that surround the
infected lung cells,” Dr. Khader says. “But what we didn’t
know was the difference between a functioning protective
granulomae, as in latent TB, and a non-protective granuloma
seen in active TB patients. We aimed to find immunologic
markers that could show us the status of the infection.”
For the study, which was funded by the National Institutes of
Health, the researchers studied human TB-infected cells as well
animal models of the disease. They found that granulomas that
contain ectopic lymphoid structures, which resemble lymph
nodes, are associated with effective suppression of TB, and that
granulomas that don’t contain them are associated with active
TB. They also learned that immune cells called T cells that had a
surface marker molecule called CXCR5 were associated with the
presence of ectopic lymphoid structures.
It’s akin to reporting a break-in, Dr. Khader says. If a person calls
911 because of a robbery, but doesn’t give a specific address, the
immune system police could come to the neighborhood but don’t
know for certain which home was invaded.
“The presence of CXCR5 provides a specific address for the
infected cells that tells the immune cells where to focus their
attention to contain the problem,” she says. “That results in the
formation of ectopic lymphoid structures and the protective
granuloma that keeps TB infection under control, unlike in active
disease. Without CXCR5, those structures did not form and active
TB was more likely.”
When the researchers delivered CXCR5 T cells from donor
animals to TB-infected mice that lacked CXCR5, T cell localization
and ectopic lymphoid structure formation was restored, leading to
decreased susceptibility to TB.
“It’s akin to reporting a break-in:
If a person calls 911 to report
a robbery but doesn't give a
specific address, the immune
system police could come to the
neighborhood but not know
which home was invaded.”
Shabaana A. Khader, PhD
Team Finds Molecule That Polices TB Infection
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