In a paper published in PLoS Medicine, Martin Holland and colleagues from the London School of Hygiene and Tropical Medicine have studied the human immune response to this infection in a population where trachoma is very common.

The researchers studied 345 children in the Gambia, who could be divided into four groups based on infection with C. trachomatis and clinical signs. Some children--particularly the older ones--were uninfected and had no clinical signs. Others were infected but showed no clinical signs--these children were incubating the bacteria. Some were infected and had clinical disease; these children had the highest bacterial loads. Finally, children recovering from an infection carried no bacteria but still had some clinical signs. The researchers detected different types of immune response in each of these groups.

Children incubating the bacteria had a strong pro-inflammatory response--their immune systems were trying to fight off infection. The pro-inflammatory response was even stronger in the infected children with clinical signs, but the regulatory response was also increased, presumably to limit inflammation. In children in the recovery phase, only regulatory immune cells, which were making mRNA from a gene called FOXP3, remained active.

These results suggest that the interaction between the infection and the clinical disease process is complex and that regulatory immune cells are important in limiting the inflammatory response to this infection. This information about immune responses at different stages of infection with C. trachomatis may help in the design of vaccines to prevent this infection.

plosmedicine

Careful examination of embryos treated with different doses of copper-blocking drugs or for different lengths of time uncovered a hierarchy of copper distribution within the developing embryo. For example, a 10 min drug treatment resulted in absence of pigment but a normal notochord. Extending the treatment to 20 min resulted in loss of pigment and a clearly abnormal notochord, and by 60 min, the treatment led to still other defects.

The team then screened mutant zebrafish for defects like those caused by copper deficiency, identifying one with a "striking resemblance--particularly in its lack of melanin pigment and wavy notochord--to the chemically induced copper-deficient" animals. The zebrafish harbored a mutation in the copper transport gene ATP7A that underlies Menkes disease, the researchers reported. They further showed that insertion of a normal human copy of the ATP7A gene reversed the development defects in the mutant fish.

The discovery of the Menkes fish will now permit screens of pharmaceutical compounds that restore copper enzyme function in the setting of a deficiency of ATP7A, the researchers said. Such drugs would be of immediate clinical relevance for treating Menkes disease.

Similar studies in zebrafish that examine the role of other gene-nutrient interactions in early human development could ultimately lead to improvements in prenatal care with the capacity to reduce the risk of birth defects, the researchers said.

"While it will require an enormous amount of science, this is the first time it is even within our grasp to know how an individual woman's genes might affect her nutritional requirements and the risk that her children might develop a congenital disorder," Gitlin said. "Ultimately, that information could allow us to provide for every woman a recipe for what is right for her pregnancy."

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