Scientists have discovered a signaling pathway that links an arthropod parasite with its host, in which molecules in the host animal's blood trigger the development and immunity of a parasite. When ticks feed on mouse blood that carries the bacterial pathogen Borrelia burgdorferi, which causes Lyme disease, a mouse immune protein binds to tick cell receptors, causing organs in the tick to develop faster. An immune response is also activated long before the bacterial pathogen infects the tick. This is the first interspecies biochemical signaling pathway that's ever been identified, according to the researchers. The findings have been reported in Science.
This work has shown that species can develop biochemical dependencies on one another, and reveals a combination of immunity and development that has never been observed before. It also involved an ancient signaling pathway that is found in plant and animal cells, which cells utilize to sense and respond to their environments. The study may also reveal new targets for therapeutics or vaccines against ticks and tick pathogens.
"This adaptive flexibility of a conserved cell signaling pathway was surprising," said senior study author Utpal Pal, a professor in the Virginia-Maryland College of Veterinary Medicine at College Park. "It is remarkable that this pathway that is present in everything from sponges to humans is so flexible it can adapt to accept a [binding partner] from another distant species. This tool that everybody has is being used in a way that we didn't imagine."
There could be other cell signaling pathways that have been harnessed for new purposes in different species, and these findings could open up a new area of immunological study.
The researchers were investigating tick immunity, which is not well-understood. They exposed ticks to blood from healthy mice and mice infected with Borrelia bacteria. A protein linked to the JAK/STAT signaling pathway, which is involved in energy production was activated only in the ticks that fed on infected blood.
The investigators injected Borrelia bacteria into ticks, and found that the bacteria alone did not activate the JAK/STAT pathway. Next, the researchers collected blood from mice infected with Borrelia, and removed the bacteria. When ticks were exposed to this 'decontaminated' blood, the JAK/STAT pathway was activated once more.
A protein in the digestive systems of ticks was found to be acting as a JAK/STAT receptor. This protein evolved to bind with interferon, a molecule that is produced by the immune system when mammals are infected with a bacterial pathogen like Borrelia.
The JAK/STAT receptor and pathway also influence normal tick development, even when infected blood does not trigger the pathway. When a gene that produces the JAK/STAT receptor was eliminated from ticks, the genetically-engineered ticks were abnormal, and could not complete development; their growth was arrested.
The study authors suggested that JAK/STAT has integrated immunity and development in ticks. In an infected host, pathogenic microbes and ticks compete for nutrients, and if a tick senses infection in a blood meal, it may start quickly growing so it can consume nutrients that may soon be scarce.
"Understanding that this pathway integrates immunity and development has important implications for potential strategies to prevent tick-borne disease transmission," Pal said.
Sources: University of Maryland, Science
