This research topic will address the multiple facets of the arthropod vector-vertebrate skin interactions that determine the success of pathogen transmission and prevalence of vector-borne diseases. Arthropods vector diverse pathogens that cause disease in humans and livestock, posing a tremendous health and economic burden worldwide. Vertebrate skin poses a significant barrier to infiltration by environmental pathogens. However, a number of pathogens have evolved to utilize arthropod vectors to bypass this barrier, gaining access to the dermis of the skin through the proboscis of the vector during a blood meal. Further, after breaching this barrier, pathogens are confronted with an even more complex challenge – the rapid, but non-specific attack of the innate immune response, followed by the slower, but specialized attack of the adaptive immune response. These three participants, the host, the vector, and the pathogen, have evolved together over millennia, resulting in a fascinating series of molecular and cellular strategies by the host to prevent infection, countered by those of vector and pathogen to circumvent those strategies.
Strategic components to be considered include host microflora that colonize the vertebrate skin and may lure vectors to specific hosts, or modify the immune repertoire of the skin, representing a new area of research that might lead to novel approaches to control vector-borne diseases. Significant progress has been made in defining the “sialomes” of vector saliva that help thwart host immune responses at the vector-host interface to facilitate feeding, and simultaneously provide a safe entry point for the pathogen. Predictably, there has been a clamor to define these essential salivary components in the hope that these proteins might be vaccine targeted to derail the vector and the pathogen. However, protein redundancy inherent in the vector salivary transcriptome presents a major challenge, requiring new approaches to accelerate discovery. Finally, a nuanced interpretation of immune responses in the skin of the vertebrate host promises to unravel a better understanding of vector-host interactions central to transmission. Use of animal and humanized animal models that recapitulate the human skin promise to provide a better understanding of the vector-skin interface, and spur the design of effective vaccines for human use. A detailed molecular and cellular understanding of host-pathogen interactions within the skin, albeit only a transit point for some vector-borne pathogens, is also essential to fully understand how the pathogen evades host defenses, which is paramount to the design and development of strategies to control these diseases.
In summary, this topic will focus on the pathogen characteristics that affect fitness in the host, components of the vector sialome, the host skin microenvironment and immune system as movements in the elaborate dance among host, vector and pathogen that has been choreographed by evolution over millennia.
This research topic will address the multiple facets of the arthropod vector-vertebrate skin interactions that determine the success of pathogen transmission and prevalence of vector-borne diseases. Arthropods vector diverse pathogens that cause disease in humans and livestock, posing a tremendous health and economic burden worldwide. Vertebrate skin poses a significant barrier to infiltration by environmental pathogens. However, a number of pathogens have evolved to utilize arthropod vectors to bypass this barrier, gaining access to the dermis of the skin through the proboscis of the vector during a blood meal. Further, after breaching this barrier, pathogens are confronted with an even more complex challenge – the rapid, but non-specific attack of the innate immune response, followed by the slower, but specialized attack of the adaptive immune response. These three participants, the host, the vector, and the pathogen, have evolved together over millennia, resulting in a fascinating series of molecular and cellular strategies by the host to prevent infection, countered by those of vector and pathogen to circumvent those strategies.
Strategic components to be considered include host microflora that colonize the vertebrate skin and may lure vectors to specific hosts, or modify the immune repertoire of the skin, representing a new area of research that might lead to novel approaches to control vector-borne diseases. Significant progress has been made in defining the “sialomes” of vector saliva that help thwart host immune responses at the vector-host interface to facilitate feeding, and simultaneously provide a safe entry point for the pathogen. Predictably, there has been a clamor to define these essential salivary components in the hope that these proteins might be vaccine targeted to derail the vector and the pathogen. However, protein redundancy inherent in the vector salivary transcriptome presents a major challenge, requiring new approaches to accelerate discovery. Finally, a nuanced interpretation of immune responses in the skin of the vertebrate host promises to unravel a better understanding of vector-host interactions central to transmission. Use of animal and humanized animal models that recapitulate the human skin promise to provide a better understanding of the vector-skin interface, and spur the design of effective vaccines for human use. A detailed molecular and cellular understanding of host-pathogen interactions within the skin, albeit only a transit point for some vector-borne pathogens, is also essential to fully understand how the pathogen evades host defenses, which is paramount to the design and development of strategies to control these diseases.
In summary, this topic will focus on the pathogen characteristics that affect fitness in the host, components of the vector sialome, the host skin microenvironment and immune system as movements in the elaborate dance among host, vector and pathogen that has been choreographed by evolution over millennia.