Transcriptional Immunoprofiling at the Tick-Virus-Host Interface during Early Stages of Tick-Borne Encephalitis Virus Transmission

Frontiers in Cellular and Infection Microbiology

Santos, Rodrigo I.¹  Slovak, Mirko²  Thangamani, Saravanan²  Heinze, Dar²  Kazimirova, Maria³  Hermance, Meghan E.⁴  Widen, Steven G.⁵ 

[1] Center for Tropical Diseases, The University of Texas Medical Branch, United States;Department of Pathology, The University of Texas Medical Branch, United States;Department of Surgery, Center for Regenerative Medicine, Boston University and Boston Medical Center, United States;Institute for Human Infections and Immunity, The University of Texas Medical Branch, United States;Institute of Zoology, Slovak Academy of Sciences, Slovakia

关键词: TBEV;    Flavivirus;    tick;    Ixodes ricinus;    Cutaneous;    immune response;   

DOI  :  10.3389/fcimb.2017.00494

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

Emerging and re-emerging diseases transmitted by blood feeding arthropods are significant global public health problems. Ticks transmit the greatest variety of pathogenic microorganisms of any blood feeding arthropod. Infectious agents transmitted by ticks are delivered to the vertebrate host together with saliva at the bite site. Tick salivary glands produce complex cocktails of bioactive molecules that facilitate blood feeding and pathogen transmission by modulating host hemostasis, pain/itch responses, wound healing, and both innate and adaptive immunity. In this study, we utilized Illumina Next Generation Sequencing to characterize cutaneous immune responses to Ixodes ricinus tick transmitted tick-borne encephalitis virus (TBEV). A comparative immune gene expression analysis of TBEV-infected and uninfected tick feeding sites was performed. Our analysis reveals that ticks create an inflammatory environment at the bite site during the first 3 hours of feeding, and significant differences in host responses were observed between TBEV-infected and uninfected tick feeding. Gene-expression analysis reveals modulation of inflammatory genes after 1 and 3 hours of TBEV-infected tick feeding. Chemokines and cytokines consistent with a neutrophil-dominated immune response are prominent. Immunohistochemistry of the tick feeding site revealed that mononuclear phagocytes and fibroblasts are the primary target cells for TBEV infection and did not detect TBEV antigens in neutrophils. Together, the genomic and immunohistochemistry results suggest early cutaneous host responses to TBEV-infected tick feeding are more inflammatory than expected and highlight the importance of inflammatory chemokine and cytokine pathways in tick-borne flavivirus transmission.

【 授权许可】

CC BY