Kansas State University

MANHATTAN — Pest insects may be sickened to learn to that researchers at Kansas State University have discovered a genetic mechanism that helps compromise their immune system.

Michael Kanost, university distinguished professor of biochemistry and molecular biophysics, led a study by Kansas State University researchers that looked at how protein molecules in the blood of insects function in insects' immune system. Insects use proteins that bind to the surface of pathogens to detect infections in their body.

"For example, when a mosquito transmits a pathogen like malaria, the parasite that causes the disease spends part of its life in the mosquito's blood," Kanost said. "It is often recognized by a genetic mechanism in the mosquito's immune system, which kills the parasite. This process is important in fully understanding how insects transmit diseases and how their immune system interacts with the pathogens they are transmitting so that we can disrupt it."

Researchers studied a protein called beta-1,3-glucan recognition protein, or GRP, from the blood of a caterpillar. They found that the GRP protein binds to a carbohydrate present in the cell wall of fungi known as beta-1,3-glucan. The GRP molecules bound to this carbohydrate, then assemble to form a larger complex of proteins. This protein complex on the surface of the pathogen may form a platform for attracting and activating other proteins from the blood, triggering immune responses that help kill pathogens in an insect's blood.

The findings may lead to new ways to control disease transmission from insects to humans and animals, as well as new methods for biocontrol of agricultural insect pests. It also sheds new light on how immune systems in organisms have evolved.

The study, "Self-association of an Insect Beta-1,3-Glucan Recognition Protein Upon Binding Laminarin Stimulates Prophenoloxidase Activation as an Innate Immune Response," was recently published in the Journal of Biological Chemistry.

The research team included Daisuke Takahashi, research associate, who conducted a majority of the experiments in Kanost's lab; Ramaswamy Krishnamoorthi, associate professor of biochemistry and bimolecular physics; Huaien Dai, a doctoral graduate; and former faculty member Yasuaki Hiromasa.

The team's study revolved around the tobacco hornworm. The insect's immune system has been studied by Kanost and others for more than 30 years.

Building on the decades of research on the tobacco hornworm's immune system, researchers concentrated on particular molecules in the blood that form pathways in which one molecule activates another molecule, leading to production of chemicals that kill pathogens.

Researchers used a variety of biochemical and biophysical experiments to understand how the protein molecules assemble on the surface of the pathogen. They found that clusters of five GRP protein molecules bind to a polysaccharide, a type of carbohydrate — beta-1,3-glucan in this case — along a larger carbohydrate molecule that makes a cell wall. Their work identified the spatial orientation of the GRP proteins in the cluster and showed that the protein-carbohydrate complexes stimulate an immune response in the caterpillar.

Understanding how the biochemical mechanism activates the immune system may enable scientists to disrupt the process, Kanost said. This could reduce insects' ability to transmit diseases to humans and animals.

It may also lead to new biocontrol of pest insects, as exploiting the mechanism could weaken and even turn off insects' immune system.  

"There are fungal pathogens that are used to kill insect pests but that are harmless to humans," Kanost said. "If we understand how insect immune response fights off fungal infections, that might lead to better ways to use microbial control on the insects."

The National Institutes of Health funded the study.