Nathan Peters Lab Projects
Redefining mechanisms of protective immunity against Leishmania infection - towards a novel vaccination strategy
Infectious diseases are a major cause of morbidity, mortality and reduced economic productivity in Canada and the world. Vaccination remains the most effective public health measure to prevent infectious diseases. However, there are few vaccines against chronic infectious diseases and no vaccines against chronic parasitic diseases. Often, pathogens that establish chronic infections either manipulate their host environment or take advantage of conditions to ensure their long- term survival. Therefore, even in settings of slowly progressive chronic infection, a vaccine must mediate a rapid immune response at the outset of infection in order to prevent these pathogens from manipulating the host environment to their benefit. This project is focused on understanding the initial events of the infectious process in settings of known protective immunity. The information gleaned from this research will be employed to develop novel and unconventional vaccination strategies against chronic infections with a focus on CD4 + T cells.
Mechanisms of Leishmania dissemination and transit in the mammalian host following vector transmission
Many infectious diseases are initiated following deposition of a pathogen into the skin by an insect vector but subsequently result in systemic infection. A major factor contributing to the pathogenesis of these infections is their ability to disseminate from the skin to the draining lymph node (dLN) and other organs. Leishmania is an obligate intracellular parasite of phagocytic cells that is transmitted by the bite of an infected sand fly vector and the causative agent of leishmaniasis. Infection with Leishmania results in a spectrum of clinical manifestations ranging from localized cutaneous infection of the skin to disseminated visceral infection of the internal organs. Despite the fact that this spectrum of disease manifestations is a fundamental clinical property of leishmaniasis, how dissemination occurs is not clear and understudied. The ultimate objective of this project is to understand how pathogen dissemination occurs to better understand the pathophysiology of disease.
Defining a role for monocyte licensing in the regulation of Leishmania-specific T cell immunity following short- and long-term pre-exposure to sand fly blood feeding
Exposure to the bites of blood feeding arthropods elicits both innate and adaptive immune responses in the vertebrate host. Immunity elicited by arthropod-derived proteins can significantly influence the outcome of infection upon subsequent exposure to arthropod transmitted pathogens. However, the immunological events that occur following blood feeding, and more importantly, how these events change in the physiological setting of repeated exposure, are not well defined. The objective of this project is to gain a clearer understanding of the interactions between immune responses against arthropod-derived proteins and pathogen-specific immunity to harness the power of the immune system to prevent or treat vector-transmitted diseases.
Influence of the insect vector microbiome on vector competence and viability
The microbiota of vertebrates has a profound impact on host physiology. This project aims to extend this understanding of the role of the microbiota to arthropods, and in particular to insects that act as vectors for infectious pathogens. Insects are a critical component of our environment, playing an untold number of roles in every ecosystem on the planet. The microbiota of insects is likely to play a critical role in numerous aspects of insect physiology. Understanding how changes in the microbiota may influence insect viability, fecundity, metabolism, and susceptibility to infections is critical to anticipating how potential alterations in the microbial communities of our changing climate may impact insect populations. We are specifically interested in the role of the microbiota of insects that transmit pathogens that impact human, veterinary and wildlife health. In some cases, these infections have significant downstream impacts on the environment and represent a significant conservation issue. This project will result in a better understanding of the role of the microbiome in insect physiology and ecology and the impact of the microbiome on the ability of insect vectors to maintain the life cycle of vector transmitted pathogens. Ultimately, we wish to understand the broader ecological and environmental consequences of the insect microbiome and determine if manipulation of the insect microbiome can be employed as a vector- transmitted pathogen control methodology.