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Principal Investigator: Shahid Karim
Organization: UNIVERSITY OF SOUTHERN MISSISSIPPI
Fiscal Year: 2024
Award: $222,000
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <Address><Amblyomma><Assay><Bio-Informatics><Bioassay><Bioinformatics><Biological Assay><Biology><Blood><Blood Reticuloendothelial System><Blood leukocyte><Body Tissues><Cell Body><Cell Lineage><Cell Mediated Immunology><Cell-Mediated Immunity><Cells><Cellular Immunity><Cellular biology><Classification><Code><Coding System><Communicable Diseases><Data><Data Set><Diagnostic tests><Early Diagnosis><Encapsulated><Genes><Genetic Markers><Hard Ticks><Hardbacked Ticks><Hemocytes><Hemolymph><Immune><Immunes><Immunologic Factors><Immunological Factors><Immunology><Impairment><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Innate Immune System><Insecta><Insects><Insects Invertebrates><Invaded><Invertebrata><Invertebrates><Ixodid ticks><Ixodida><Ixodidae><Knowledge><Leukocytes><Leukocytes Reticuloendothelial System><Literature><Marrow leukocyte><Mediating><Microbe><Mission><Molecular><Molecular Fingerprinting><Molecular Profiling><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Non-Polyadenylated RNA><Outcome><Ovary><Phagocytes><Phagocytic Cell><Phagocytosis><Phase><Play><Population><Post-Transcriptional Gene Silencing><Posttranscriptional Gene Silencing><Prevalence><Preventative measure><Preventative vaccine><Preventive measure><Preventive vaccine><Prophylactic vaccine><Public Health><Publishing><R parkeri><R. parkeri><RNA><RNA Gene Products><RNA Interference><RNA Seq><RNA Silencing><RNA sequencing><RNAi><RNAseq><Reagent><Recombinant Proteins><Regulation><Research><Resolution><Ribonucleic Acid><Rickettsia><Rickettsia Infections><Rickettsia parkeri><Rickettsial Infectious Disease><Rickettsial Infectious Disorder><Rickettsiales><Rickettsiales disease><Rickettsiosis><Role><Saliva><Salivary Glands><Salivary Glands Head and Neck><Sequence-Specific Posttranscriptional Gene Silencing><Systematics><Technology><Tick-Borne Diseases><Ticks><Tissues><Transmission><Treatment Efficacy><United States><United States National Institutes of Health><Vertical Transmission><White Blood Cells><White Cell><amebocyte><antibiotic tolerance><cell biology><cell type><climate change><climatic changes><comparative><differential expression><differentially expressed><early detection><experiment><experimental research><experimental study><experiments><gene biomarker><gene expression biomarker><gene marker><gene signature biomarker><genetic biomarker><global climate change><gulf coast><hard-bodied ticks><high reward><high risk><human pathogen><immunologic substance><immunological substance><intervention efficacy><microbial><molecular profile><molecular signature><neglect><novel><pathogen><prevent><preventing><resolutions><response><rickettsial disease><scRNA-seq><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><social role><spotted fever><therapeutic efficacy><therapy efficacy><tick-borne><tick-borne illness><tick-borne pathogen><tickborne><tickborne disease><tickborne illness><tickborne pathogen><tolerance to antibiotics><tolerate antibiotics><tool><trafficking><transcriptional differences><transcriptome sequencing><transcriptomic sequencing><transmission process><vector><vector competence><vector transmission><vectorial competence><white blood cell><white blood corpuscle>