Monday, May 6, 2024
5/6/2024
Summary Tick-borne diseases, including Spotted Fever Group Rickettsiosis, are rising due to climatic changes and are predicted to increase. The increase in rickettsiosis is a significant threat to public health in the absence of preventive measures. Tick hemocytes (immune cells) are mammalian leukocytes' functional equivalent and limit ticks' capacity to transmit human pathogens through phagocytosis, encapsulation, secretion of immune factors, and immune priming. The ixodid ticks rely on an efficient innate immune system for protection against invading microbes, in which hemocytes play a crucial role. Tick cellular immunity is primarily a neglected and unexplored field of vector biology. A complete understanding of the immune factors involved in the interactions between ticks and tick-borne pathogens in hemocytes is crucial to elucidate their role in vector competence and to help identify novel targets for developing new strategies to block pathogen transmission. This study aims to build technologies by realizing the potential of exploiting tick hemocyte biology. We began addressing this need, and our compelling preliminary data show the immune cell types and complexity in the uninfected and Rickettsia parkeri-infected ticks. Bulk RNA-seq analysis of uninfected and infected tick hemocytes showed that out of 39,429 coding sequences, 7.3% were differentially expressed and classified as related to immune genes. We hypothesize that Rickettsia parkeri manipulates the Amblyomma maculatum phagocytic immune cells to facilitate systemic dissemination and enhance vertical transmission. To address these questions, we will examine Amblyomma maculatum immune cell populations from uninfected and infected (Rickettsia parkeri-infected) conditions through the following specific aims: 1) To generate single-cell RNA sequencing from uninfected and Rickettsia parkeri-infected hemocytes for downstream analyses, and 2) To dissect the role of hemocyte-specific marker genes in cellular immunity and vector competence by RNA interference approach. In this high-risk, high-reward application, these aims will provide critical reagents, tools, and data to address critical gaps in fundamental knowledge of tick immune cell biology and vector competence. These studies will provide critical data to address gaps in fundamental knowledge of tick immune cell biology and vector competence. This exploratory project will also provide an opportunity to develop new tools to study hemocyte biology. Additionally, the outcome of this project could be extrapolated to other tick species of public health significance and is expected to provide a critical comparative understanding of invertebrate immunology.
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