Murine Dendritic Cells Responding to Bacterial Biomarkers, Lipopolysaccharide and Teichoic Acid

Arthropod vectors transmit pathogens responsible for 17% of global human infectious diseases. Most of these pathogens are transmitted within vector saliva during blood feeding. Ticks transmit bacteria, rickettsia, viruses, and protozoans, and are vectors of the greatest variety of zoonotic diseases affecting humans and animals. Previous research documented the presence of acetylcholinesterase (AChE) in saliva of ticks, mosquitoes, sand flies, and biting midges, each of which exhibited Michaelis-Menten KM values lower than the KM value for bovine serum AChE (a model for mammalian AChE). A lower KM value is indicative of higher substrate affinity, consistent with a hypothesized role to deplete host tissue acetylcholine and modulate cellular immune responses at the vector bite site. We hypothesized that arthropod vector salivary cholinesterase activity could: 1) decrease toxicity of acetylcholine in the large blood meal, 2) modulate host immune responses to facilitate tick parasitism, and 3) facilitate salivary-assisted transmission of vector-borne pathogens. Consistent with this hypothesis, we report differential transcript expression resulting from presence of catalytically-active recombinant tick AChE by murine dendritic cell cultures responding to immune stimulation by the bacterial biomarkers, lipopolysaccharide and teichoic acid. The presented evidence is consistent with the hypothesis that salivary AChE of ticks or other vectors may act as a regulator of tissue acetylcholine at the vector bite site, resulting in modulation of host inflammatory and other immune responses. It is suggested that further research incorporating multiple cell types and utilizing flow cytometry and single cell RNA-Seq would provide greatly improved data to reveal identity of first responders, sequence of cellular responses and cell interactions, as well as identifying transcript expression and immune pathways affected by presence of vector salivary AChE.