Potential Role of Salivary Cholinesterase in Salivary-assisted Transmission of Pathogens by Arthropod Vectors

The present study is intended to test the hypothesis that salivary acetylcholinesterase (AChE) present in arthropod vectors may modulate the immune response of host animals by depletion of acetylcholine at or near the bite site, thereby participating in the mechanism of salivary assisted transmission (SAT) and establishment of pathogens in the host. Specifically, we are testing the hypothesis that arthropod salivary AChE may alter the immune response to bacterial peptidoglycan (LPS) in mouse dendritic cells. Dendritic cells are primary immune sentinels and antigen presenting cells located in mammalian skin. Tissue damage and introduction of foreign antigens (including arthropod saliva and potential pathogens) is incurred due to bites of hematophagous arthropods. The saliva of arthropods that vector agents of infectious disease is known to facilitate pathogen transmission and establishment in the host, however the mechanism for this salivary assisted transmission (SAT) has not been elucidated. Many mammalian cell types, including most immune cells are cholinergically competent, secrete acetylcholine when activated, and are responsive to acetylcholine released systemically, or by autocrine or paracrine signaling. Recent research in our laboratory has found acetylcholine hydrolyzing activity (hereafter referred to as acetylcholinesterase, AChE) in saliva of arthropod vectors including, ticks, mosquitoes, sand flies, and possibly biting midges, but not in saliva of the non-vector hematophagous arthropods, horn flies or stable flies and is also absent in house flies. These findings are consistent with the hypothesis that salivary AChE present in arthropod vectors may modulate the immune response of host animals by depletion of acetylcholine at or near the bite site, thereby participating in the mechanism of salivary assisted transmission (SAT) and establishment of pathogens in the host.