Tick Anti-Inflammatory Proteins

Arthropod saliva possesses anti-hemostatic, anesthetic, and anti-inflammatory properties that facilitate feeding and, inadvertently, dissemination of pathogens. Recently, several vector-borne pathogens have been shown to induce nod-like receptor (NLR) activation in immune cells. NLRs are innate immune pattern recognition molecules involved in detecting microbial molecules and danger signals. Nod1/2 signaling results in activation of the nuclear factor (NF)-κB and the mitogen-activated protein (MAP) kinase pathways. Caspase-1 NLRs regulate the inflammasome - a protein scaffold that governs the maturation of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. We focus on the discovery of tick proteins that counters nod-like receptor (NLR) sensing upon pathogen infection. We also elaborate on the possible anti-inflammatory properties of tick proteins as therapeutic drugs against chronic sterile diseases.

The Tick Immune System

The increase in knowledge observed for arthropod-pathogen interactions in the past decade can be directly correlated to the availability of multiple sequenced insect genomes. Comparative genomics analysis coupled to functional assays uncovered evolutionarily conserved signaling pathways and provided important insights towards the understanding of insect immunity. However, extrapolating this approach to non-insect arthropods, such as the tick Ixodes scapularis, sometimes constitutes a problem because of the lack of distinguishable protein homologues and incorrect annotation of genes due to low sequence coverage or incompleteness of a particular genome. We are studying the non-canonical immune deficiency (IMD) signaling pathway of the Lyme disease tick I. scapularis. We are characterizing this signaling relay based on biochemical, molecular and structural biology information. This novel immune pathway in ticks has broad implications for the arthropod biology community.

Lipid Immunomodulators

Lipids exhibit an immense combinatorial and structural diversity due to the complexity of head groups, acyl chains, and backbone structures. They are also critically important for an immune response against a microbial pathogen. Through a mass spectrometric lipidomics approach, we discovered bacterial bioactive molecules that affect cytokine secretion upon infection. We are currently performing refined chemistry coupled to direct spatial visualization to identify bacterial lipids that affect inflammation. We are also focused on the host eicosanoid signaling. We observed that macrophages secrete prostaglandins upon bacterial stimulation, and inhibition of cyclooxygenases hampers the production of pro-inflammatory cytokines. Therefore, we are characterizing the prostaglandin signaling pathway and identifying host lipid immunomodulators upon bacterial infection. This research should identify lipid biomarkers that may distinguish pathogenic bacteria and unravel the role of lipid mediators in acute inflammation.








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