Tick innate immune response to pathogen infection at single-cell resolution

Ticks rely on robust cellular and humoral immunity to control pathogen infection. However, a tick’s innate immune system is a complex black box comprised of immune cells (called hemocytes), known to play a significant role in both cellular and humoral responses toward pathogens. Despite the importance of hemocytes in regulating microbial infection, understanding their basic biology and molecular mechanisms remains limited. 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 examined the tick hemocyte heterogeneity at the transcriptomic level. We used the 10X genomics single-cell RNA sequencing platform to analyze their transcriptome at a unique level in unfed, partially blood-fed, and pathogen-infected hemocytes. We were able to show the presence of seven distinct hemocyte transcriptomic populations in the tick vector. Our results revealed that clusters representing granulocyte and oenocytoids populations are increased with pathogen infection. This work opens a new field of tick innate immune biology to understand the role of hemocytes, particularly in response to prolonged blood-feeding (hematophagy) and tick-pathogen interactions.