The insect immune deficiency (IMD) pathway resembles the tumour necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties activate the IMD signalling cascade remains unknown. Here, we show that infection-derived lipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 1-palmitoyl-2-oleoyl diacylglycerol (PODAG) stimulate the IMD pathway of ticks. The tick IMD network protects against colonization by three distinct bacteria, that is the Lyme disease spirochete Borrelia burgdorferi and the rickettsial agents Anaplasma phagocytophilum and A. marginale. Cell signalling ensues in the absence of transmembrane peptidoglycan recognition proteins and the adaptor molecules Fas-associated protein with a death domain (FADD) and IMD. Conversely, biochemical interactions occur between x-linked inhibitor of apoptosis protein (XIAP), an E3 ubiquitin ligase, and the E2 conjugating enzyme Bendless. We propose the existence of two functionally distinct IMD networks, one in insects and another in ticks.

Background: Anaplasma phagocytophilum (Ap) is an obligate intracellular bacterium and the agent of human granulocytic anaplasmosis, an emerging tick-borne disease. Ap alternately infects ticks and mammals and a variety of cell types within each. Understanding the biology behind such versatile cellular parasitism may be derived through the use of tiling microarrays to establish high resolution, genome-wide transcription profiles of the organism as it infects cell lines representative of its life cycle (tick; ISE6) and pathogenesis (human; HL-60 and HMEC-1). Results: Detailed, host cell specific transcriptional behavior was revealed. There was extensive differential Ap gene transcription between the tick (ISE6) and the human (HL-60 and HMEC-1) cell lines, with far fewer differentially transcribed genes between the human cell lines, and all disproportionately represented by membrane or surface proteins. There were Ap genes exclusively transcribed in each cell line, apparent human- and tick-specific operons and paralogs, and anti-sense transcripts that suggest novel expression regulation processes. Seven virB2 paralogs (of the bacterial type IV secretion system) showed human or tick cell dependent transcription. Previously unrecognized genes and coding sequences were identified, as were the expressed p44/msp2 (major surface proteins) paralogs (of 114 total), through elevated signal produced to the unique hypervariable region of each – 2/114 in HL-60, 3/114 in HMEC-1, and none in ISE6. Conclusion: Using these methods, whole genome transcription profiles can likely be generated for Ap, as well as other obligate intracellular organisms, in any host cells and for all stages of the cell infection process. Visual representation of comprehensive transcription data alongside an annotated map of the genome renders complex transcription into discernable patterns.

Ticks and tick-borne diseases are a significant economic hindrance for livestock production and a menace to public health. The expansion of tick populations into new areas, the occurrence of acaricide resistance to synthetic chemical treatments, the potentially toxic contamination of food supplies, and the difficulty of applying chemical control in wild-animal populations have created greater interest in developing new tick control alternatives. Plant compounds represent a promising avenue for the discovery of such alternatives. Several plant extracts and secondary metabolites have repellent and acaricidal effects. However, very little is known about their mode of action, and their commercialization is faced with multiple hurdles, from the determination of an adequate formulation to field validation and public availability. Further, the applicability of these compounds to control ticks in wild-animal populations is restrained by inadequate delivery systems that cannot guarantee accurate dosage delivery at the right time to the target animal populations. More work, financial support, and collaboration with regulatory authorities, research groups, and private companies are needed to overcome these obstacles. Here, we review the advancements on known plant-derived natural compounds with acaricidal potential and discuss the road ahead toward the implementation of organic control in managing ticks and tick-borne diseases.

Ticks transmit a variety of human pathogens, including Borrelia burgdorferi, the etiological agent of Lyme disease. Multiple pathogens that are transmitted simultaneously, termed “coinfections”, are of increasing importance and can affect disease outcome in a host. Arthropod immunity is central to pathogen acquisition and transmission by the tick. Pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) and induce humoral responses through the Toll and Immune Deficiency (IMD) pathways. Comparative analyses between insects and ticks reveal that while the Toll pathway is conserved, the IMD network exhibits a high degree of variability. This indicates that major differences in humoral immunity exist between insects and ticks. While many variables can affect immunity, one of the major forces that shape immune outcomes is the microbiota. In light of this, we discuss how the presence of commensal bacteria, symbionts and/or coinfections can lead to altered immune responses in the tick that impact pathogen persistence and subsequent transmission. By investigating non-insect arthropod immunity, we will not only better comprehend tick biology, but also unravel the intricate effects that pathogen coinfections have on vector competence and tick-borne disease transmission.

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles fromIxodes scapularisenable tick feeding and promote infection of the mildly virulent rickettsial agentAnaplasma phagocytophilumthrough the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tickDermacentor andersonimitigate microbial spreading caused by the lethal pathogenFrancisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.