How relevant are in vitro culture models for study of tick-pathogen interactions?

Abstract

Although tick-borne infectious diseases threaten human and animal health worldwide, with constantly increasing incidence, little knowledge is available regarding vector-pathogen interactions and pathogen transmission. In vivo laboratory study of these subjects using live, intact ticks is expensive, labor-intensive, and challenging from the points of view of biosafety and ethics. Several in vitro models have been developed, including over 70 continuous cell lines derived from multiple tick species and a variety of tick organ culture systems, facilitating many research activities. However, some limitations have to be considered in the translation of the results from the in vitro environment to the in vivo situation of live, intact ticks, and vertebrate hosts. In this review, we describe the available in vitro models and selected results from their application to the study of tick-borne viruses, bacteria, and protozoa, where possible comparing these results to studies in live, intact ticks. Finally, we highlight the strengths and weaknesses of in vitro tick culture models and their essential role in tick-borne pathogen research.

Anaplasma marginale Infection of Dermacentor andersoni Primary Midgut Cell Culture Is Dependent on Fucosylated Glycans

“…Successful establishment of infection by the pathogen requires adhesion to the midgut cell which is key for subsequent cellular invasion, intracellular multiplication, and dissemination to other tick organs, including salivary glands for the successful transmission of the pathogen. A cell culture system derived from tick midgut tissue is crucial to address the role of tick fucosylated glycans for the infection of midgut cells ( Salata et al., 2021 ). Attachment to the host cell via glycans is a common strategy employed by bacteria and viruses during the establishment of an infection within the host ( Ilver et al., 1998 ; Pedra et al., 2010 ; Chen et al., 2011 ; Varki, 2017 ; Heim et al., 2019 ; Suwandi et al., 2019 ).…”

“…To study A. marginale and tick midgut cell interactions at the cellular and molecular levels, an in vitro tick midgut cell culture is required. Most currently available tick cell lines were isolated from embryonated eggs containing multiple cell types which may not include differentiated midgut cells ( Bell-Sakyi, 1991 ; Munderloh et al., 1994 ; Bell-Sakyi et al., 2018 ; Lima-Duarte et al., 2021 ; Salata et al., 2021 ). Heretofore, the lack of available tick cell culture systems derived from midgut has precluded the in vitro investigation of A. marginale -tick midgut cell interactions.…”

New Cell Lines Derived from European Tick Species

“…Despite several attempts using tropical bovine parasites [69,70], no in vitro culture system for continuous propagation of any Babesia sp. in tick cells has yet been developed [10]. As Babesia spp.…”

“…Tick cell lines form an increasingly valuable part of the toolkit for research on the biology and control of ticks and tick-borne pathogens [5][6][7][8][9][10]. However, historically, much of the cell culture-based research has utilised cell lines derived from non-European ticks, such as the tropical species Rhipicephalus appendiculatus and Rhipicephalus microplus, and the North American species Ixodes scapularis.…”

Virus-Derived DNA Forms Mediate the Persistent Infection of Tick Cells by Hazara Virus and Crimean-Congo Hemorrhagic Fever Virus

“…To date, very limited information is available about the replication and persistence of CCHFV in ticks due to the 4 requirement for the virus to be handled in high-containment laboratories, compounded by the difficulty in manipulation of infected ticks in a biosafety level (BSL)-4 facility (7,8). However, we have recently developed a CCHFV infection model based on embryo-derived Hyalomma anatolicum cell lines, providing the opportunity to study virus-vector interaction in an easier-tohandle in vitro system (9,10).…”