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Mosquito Saliva Enough to Cause Disruption in Immune Response

Over 750,000 people die of mosquito transmitted diseases every year, such as malaria, dengue, West Nile, Zika, and chikungunya fevers.  Since the host ranges of species of mosquitoes grow because of climate change, the prevalence of these disorders is expected to rise further in the oncoming decades.  Not only do these mosquitoes carry diseases, but they also nearly always increase the intensity of the diseases that they transmit.

Mosquito saliva is an intricate combination of proteins which makes it possible for the mosquito to get a blood meal out of its own host (required for egg maturation), by imitating vasoconstriction, platelet aggregation, coagulation, and inflammation.  It’s well-known that mosquito saliva Includes proteins which are immunogenic to people, and a few allergic reactions can be quite severe.

Now, a group of investigators at Baylor College of Medicine have taken a closer look at the impact of mosquito saliva independently and discovered it can activate an unexpected range of immune reactions in an animal model of the human immune system.  These results offer a chance to create effective strategies to stop mosquito-based transmission of illness.

Billions of people worldwide are exposed to diseases transmitted by mosquitoes, and many of these conditions do not have effective treatments,

” said corresponding author Dr. Rebecca Rico-Hesse, professor of molecular virology and microbiology at Baylor College of Medicine. “One of the interests of my lab is to study the development of dengue fever, which is caused by the dengue virus transmitted by mosquito Aedes aegypti.”

In 2012, we demonstrated in these humanized mice that mosquito-bite delivery and needle-injection delivery of dengue virus led to significantly different disease developments,” Rico-Hesse said. “Importantly, mosquito-bite delivery of the virus resulted in a more human-like disease than the one we observed after needle-injection delivery of the virus. When the mosquitoes delivered the virus, the mice had more of a rash, more fever and other characteristics that mimic the disease presentation in humans.”

To check the impact of virus-free mosquito spit on humanized mice, the investigators held that a vial containing mosquitoes from a footpad of anesthetized humanized mice, allowing a total of four parasites to feed both footpads.

They then examined blood and quite a few additional tissue samples, 24 hours and seven days following the mosquitoes bit that the mice, also determined the amounts of cytokines, molecules which regulate the immune response, in addition to the amount and action of different kinds of immune cells.  They compared these results with those obtained by humanized mice which hadn’t been bitten by mosquitoes.

We found that mosquito-delivered saliva induced a varied and complex immune response we were not anticipating,” said co-author Dr. Silke Paust, assistant professor of pediatrics at Baylor and Texas Children’s Hospital. “For instance, both the immune cell responses and the cytokine levels were affected. We saw activation of T helper cells 1, which generally contribute to antiviral immunity, as well as activation of T helper cells 2, which have been linked to allergic responses.”

The diversity of the immune response was most striking to me. This is surprising given that no actual infection with any type of infectious agent occurred,” said Paust, who also is a member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine. “These results are evidence that components in the mosquito saliva can modulate the immune response in humanized mice.”

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