Tick Immune System: What Is Known, the Interconnections, the Gaps, and the Challenges

Abstract

Ticks are ectoparasitic arthropods that necessarily feed on the blood of their vertebrate hosts. The success of blood acquisition depends on the pharmacological properties of tick saliva, which is injected into the host during tick feeding. Saliva is also used as a vehicle by several types of pathogens to be transmitted to the host, making ticks versatile vectors of several diseases for humans and other animals. When a tick feeds on an infected host, the pathogen reaches the gut of the tick and must migrate to its salivary glands via hemolymph to be successfully transmitted to a subsequent host during the next stage of feeding. In addition, some pathogens can colonize the ovaries of the tick and be transovarially transmitted to progeny. The tick immune system, as well as the immune system of other invertebrates, is more rudimentary than the immune system of vertebrates, presenting only innate immune responses. Although simpler, the large number of tick species evidences the efficiency of their immune system. The factors of their immune system act in each tick organ that interacts with pathogens; therefore, these factors are potential targets for the development of new strategies for the control of ticks and tick-borne diseases. The objective of this review is to present the prevailing knowledge on the tick immune system and to discuss the challenges of studying tick immunity, especially regarding the gaps and interconnections. To this end, we use a comparative approach of the tick immune system with the immune system of other invertebrates, focusing on various components of humoral and cellular immunity, such as signaling pathways, antimicrobial peptides, redox metabolism, complement-like molecules and regulated cell death. In addition, the role of tick microbiota in vector competence is also discussed.

Unpacking the intricacies of Rickettsia–vector interactions

“…However, further investigation is needed to understand the physical state and active mechanisms utilized by rickettsiae during arthropod infection. While several mechanisms of innate immunity in arthropod vectors have been identified [40], their exact role during species-specific infection remains unknown. Differential activity of AMPs, when exposed to pathogens versus endosymbionts, presents a specific recognition in the tick background [41,42].…”

“…Still undetermined is the specificity of rickettsiae-vector relationships guiding the balance between inhibiting infection and widespread dissemination in the vector. However, recently compiled arthropod genomes have armed the field with the capacity to utilize techniques, such as RNA interference (RNAi) and CRISPR-Cas9, in arthropods to enhance our understanding of factors driving vector competence [40,43].…”

“…In addition to vectors' chitinous exoskeleton, resident microflora can also defend against invading microorganisms. The role of endosymbionts in the transmission of vector-borne pathogens has gained increased attention due to their ability to alter an arthropod's vectorial capacity [40,43,80]. The influence of the microbiome in altering rickettsial vector immunity and metabolism is being assessed [53].…”

Resistance to Ticks and the Path to Anti-Tick and Transmission Blocking Vaccines

“…Ferritin based anti-tick vaccines did not induce bovine resistance to Ixodes ricinus infestation [ 181 ] but did stimulate a significant drop in engorgement weights in adult Haemaphysalis longicornis infesting immunized rabbits [ 238 ]. Tick innate immune defense signaling pathways, soluble molecules, hemocytes, and complement-like molecules are an additional complex of targets for anti-tick and tick-borne pathogen transmission blocking vaccines [ 239 ].…”

Ticks: More Than Just a Pathogen Delivery Service

“…A secondary barrier to colonization is the tick immune system ( Oliva Chávez et al, 2017 ; Fogaça et al, 2021 ). Some immune pathways are described as restricting vector-borne microbes, such as the Immune Deficiency pathway ( Rosa et al, 2016 ; Capelli-Peixoto et al, 2017 ; Shaw et al, 2017 ; Carroll et al, 2019 ), the JAK-STAT pathway ( Liu et al, 2012 ; Smith et al, 2016 ), the RNAi pathway ( Rückert et al, 2014 ; Schnettler et al, 2014 ; Grubaugh et al, 2016 ; Hart and Thangamani, 2021 ), and phagocytic hemocytes ( Coleman et al, 1997 ; Dunham-Ems et al, 2009 ; Talactac et al, 2021 ); however, vectored pathogens are still able to colonize the tick.…”