RIVERSIDE, Calif. – Summer for most people means time spent outdoors, which could also mean increased exposure to bugs and, possibly, arthropod-borne diseases, such as “rickettsial diseases” – infectious diseases spread by bacteria, which, generally, are transmitted by lice, fleas, ticks and mites.
Now a $1.6 million grant from the National Institutes of Health (NIH) will enable an entomologist at the University of California, Riverside to study how our immune system responds to rickettsial infection.
The immune system is composed of innate and adaptive immunity. The first line of war against infectious agents is innate immunity, while adaptive immunity acts as a second line of defense and protects us against re-exposure to the same pathogen.
“If we understand how our innate immune system works during rickettsial infection, we can use this knowledge to devise novel therapeutics that delay or prevent the onset of rickettsial diseases,” said Joao Pedra, the principal investigator of the five-year grant and an assistant professor of entomology.
The main types of rickettsial diseases include devastating typhus, spotted fever, and tsutsugamushi disease. Fever, chills, aches and pain are some common clinical symptoms.
Rickettsial diseases tend to be endemic in areas where public health infra-structure is poor or in tropical regions – typically, the developing world. But because of climate change, arthropod vectors that transmit rickettsial agents have re-emerged in developed countries such as the United States.
In the past few decades, research has shown that blood-sucking arthropods such as ticks, mosquitoes, and lice use their saliva during feeding to dampen inflammation and coagulation, and decrease the pain associated with the bite. Consequently, when a person gets bitten by a tick, he or she does not feel pain and blood does not coagulate. The result is that the immune system, caught unawares, is unable to get rid of the tick.
“Pathogens take advantage of these salivary properties to colonize the mammalian host,” Pedra said. “Essentially, they have a ‘free-pass’ for infection. Our project will study how one tick salivary protein affects the immune system and facilitates pathogen colonization to the mammalian host.”
Past research in Pedra’s lab has shown that the Lyme disease tick uses the anti-inflammatory properties of saliva to dampen the immune response during feeding. The rickettsial agent Anaplasma phagocytophilum – a human pathogen – uses one protein present in the tick saliva to colonize the mammalian host. This protein knocks down the immune system during tick feeding. A. phagocytophilum takes advantage of this development and colonizes the host, causing disease.
“One mystery we would like to solve is why rickettsial agents are so successful in colonizing mammals,” Pedra said. “Uncovering the mechanistics of tick salivary immune evasion will help us pinpoint which pathways are important for therapeutic development against rickettsial diseases.”
An expert on rickettsial diseases, Pedra first became interested in the interaction between bacterial pathogens and the immune system when he was a postdoctoral scholar in microbiology and immunology at the Yale University School of Medicine.
“In this research project, we will investigate how the rickettsial pathogen ‘cheats’ the immune system at the tick-host interface,” he said. “To understand this, we first will investigate the biology of the tick, the pathogen, and the mammalian host. And we will explain how the immune system responds to the pathogen.”
Pedra will be joined in the research by two UC Riverside graduate students, some undergraduates and one technician. This is a collaborative effort with Michail Kotsyfakis at the Institute of Parasitology in the Czech Republic. Kotsyfakis, a biochemist who has worked extensively on tick-borne diseases, was the first to characterize the role of the tick salivary protein involved in this study, and will receive approximately $125,000 of the NIH grant to produce the molecule.
Originally from Brazil, Pedra received his doctoral degree in entomology from Purdue University, Ind. He was an associate research scientist at the Yale University School of Medicine before he joined UCR in 2009. He is a recipient of a career award in public health from the Centers for Disease Control and Prevention.