Experimental Babesia rossi infection induces hemolytic, metabolic, and viral response pathways in the canine host
| Autor: | Justin B. Lack, Arun K. Boddapati, Hans Ackerman, Rachel Lillian Smith, Andrew L. Leisewitz, Amelia Goddard, Steven David Brooks, Johan P. Schoeman |
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| Rok vydání: | 2021 |
| Předmět: |
Population
Babesia Disease QH426-470 Babesia rossi Hemolysis Canine host Pathogenesis Immune system Dogs Time course RNA-seq Babesiosis Genetics Animals Dog Diseases education Africa South of the Sahara education.field_of_study Innate immune system biology Host response to infection Research Acquired immune system biology.organism_classification Immunology Emerging infectious disease Hemoprotozoan parasite TP248.13-248.65 Biotechnology |
| Zdroj: | BMC Genomics BMC Genomics, Vol 22, Iss 1, Pp 1-16 (2021) |
| ISSN: | 1471-2164 |
| Popis: | BackgroundBabesia rossiis a leading cause of morbidity and mortality among the canine population of sub-Saharan Africa, but pathogenesis remains poorly understood. Previous studies ofB. rossiinfection were derived from clinical cases, in which neither the onset of infection nor the infectious inoculum was known. Here, we performed controlledB. rossiinoculations in canines and evaluated disease progression through clinical tests and whole blood transcriptomic profiling.ResultsTwo subjects were administered a low inoculum (104parasites) while three received a high (108parasites). Subjects were monitored for 8 consecutive days; anti-parasite treatment with diminazene aceturate was administered on day 4. Blood was drawn prior to inoculation as well as every experimental day for assessment of clinical parameters and transcriptomic profiles. The model recapitulated natural disease manifestations including anemia, acidosis, inflammation and behavioral changes. Rate of disease onset and clinical severity were proportional to the inoculum. To analyze the temporal dynamics of the transcriptomic host response, we sequenced mRNA extracted from whole blood drawn on days 0, 1, 3, 4, 6, and 8. Differential gene expression, hierarchical clustering, and pathway enrichment analyses identified genes and pathways involved in response to hemolysis, metabolic changes, and several arms of the immune response including innate immunity, adaptive immunity, and response to viral infection.ConclusionsThis work comprehensively characterizes the clinical and transcriptomic progression ofB. rossiinfection in canines, thus establishing a large mammalian model of severe hemoprotozoal disease to facilitate the study of host-parasite biology and in which to test novel anti-disease therapeutics. The knowledge gained from the study ofB. rossiin canines will not only improve our understanding of this emerging infectious disease threat in domestic dogs, but also provide insight into the pathobiology of human diseases caused byBabesiaandPlasmodiumspecies. |
| Databáze: | OpenAIRE |
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