UC Riverside-led research could lead to new
therapies for parasitic worm infections currently afflicting an
estimated two billion people worldwide.
Worm infections represent a
major global public health problem, leading to a variety of
debilitating diseases and conditions, such as anemia, elephantiasis,
growth retardation and dysentery. Several drugs are available to treat
worm infections, but reinfection is high especially in developing
countries.
Now, scientists at the University of California, Riverside and colleagues around the world have made a discovery, reported in this month’s issue of PLOS Pathogens,
that could lead to more effective diagnostic and treatment strategies
for worm infections and their symptoms. The researchers found that
resistin, an immune protein commonly found in human serum, instigates an
inappropriate inflammatory response to worm infections, impairing the
clearance of the worm.
“Targeting this inflammatory pathway with drugs or antibodies could
be a new therapeutic strategy to treat worm infections and the
associated pathology,” said Meera Nair, an assistant professor of biomedical sciences in the UC Riverside School of Medicine,
whose laboratory made the discovery. “Additionally, our data point to
the diagnostic potential for resistin as a new biomarker for impaired
immune responses to worms.”
Jessica Jang, the lead author of the research paper and a third-year
UCR graduate student in microbiology, explained that resistin regulates
the recruitment of innate immune cells called monocytes to the site of
infection to produce inflammatory cytokines (small proteins that are
important in cell signaling).
“Future work in my Ph.D. research will focus on further investigating
the activation of monocytes so we can clinically exploit this immune
pathway,” she said.
Parasitic worms, known scientifically as helminths, include filarial
worms and hookworms. They cause diseases such as elephantiasis, which
produces extreme swelling of extremities, and necatoriasis, which causes
abdominal pain, diarrhea and weight loss. The infections are often
associated with life-long morbidity, including malnutrition, growth
retardation and organ failure.
In many developing countries where parasitic worms are prevalent due
to substandard sanitation facilities, infections in humans are common,
as are reinfections. Some infected patients develop immunity, but others
remain susceptible to infections when they are re-exposed or develop
chronic infections. Currently, no vaccine is available against human
worm pathogens.
The research directed by Nair’s lab combined mouse studies with human
data to demonstrate that resistin is actually detrimental, causing
excessive inflammation that impedes the body’s ability to clear
parasitic worms.
In the animal studies, mice containing the gene expressing human
resistin and infected with a parasitic worm similar to the human
hookworm experienced excessive inflammation, leading to increased weight
loss and other symptoms. Clinical samples from two groups of
individuals from the south Pacific island of Mauke and from Ecuador –
one group infected with filarial worms causing lymphatic filariasis and a
second group infected with intestinal roundworms Ascaris – revealed
increased levels of resistin in the infected individuals compared to
those who were uninfected or immune.
A better understanding of human resistin may also reveal new
knowledge about obesity and diabetes. Resistin has been mapped to the
pathway of immune-mediated inflammation that promotes diabetes and other
obesity-related disorders and Nair hopes to combine her lab’s basic
science expertise with the developing clinical research enterprise in
the UCR medical school as a future avenue to research new diagnostic or
treatment strategies.
Collaborating in the study were scientists from: the Malaghan
Institute of Medical Research in New Zealand; Pontificia Universidad
Católica del Ecuador in Quito, Ecuador; St. George’s University of
London; the Laboratory of Parasitic Diseases at the National Institutes
of Health; and the Perelman School of Medicine at the University of
Pennsylvania.
Funding for the research at UCR was provided by the National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health, the Division of Biomedical Sciences (UCR School of Medicine)
and a UCR Academic Senate Regents Faculty Fellowship.