Is Arthropod Saliva the Achilles’ Heel of Vector-Borne Diseases?

establishment of a vector-borne disease. For example, tick-derived saliva factors appear to inhibit inflammatory cytokine secretion thus preventing efficient immune responses against tick-borne Rickettsia (4); a defined molecule in the saliva of the Aedes aegypti mosquito (SAAG-4) has the potential to alter the Th-profile of the bite-induced immune response likely rendering the host unable to effectively eliminate vectorborne viruses (5); and sand fly saliva has a caspase-dependent, pro-apoptotic effect on neutrophils resulting in an infection of the host with increased numbers of Leishmania parasites (6). Vector saliva can even exhibit its effect on the course of an infection when delivered separately from the infectious inoculum, as demonstrated by the injection of purified Plasmodium parasites followed by the bite of a non-infected mosquito and thus the delivery of salivary proteins in “trans” (7). Finally, even a temporal separation of salivaand pathogen-delivery cannot eliminate effects of arthropod saliva on a subsequent infection with a vector-borne disease (8). Numerous reports have documented the potent and pleiotropic effects of the saliva of blood-feeding arthropods, which include anti-coagulation, vasodilation anti-inflammation [reviewed by (9)], calling into question how minute amounts of proteins in the inoculum that is delivered during a blood meal could significantly alter the host’s immune response against the vector-delivered pathogen. This observation is particularly puzzling considering that vector saliva primarily evolved to assist the arthropod in obtaining a blood meal and not to facilitate the infection of the vertebrate host with a vector-borne pathogen. The main effect of immunomodulatory saliva components in regard to infection appears to be temporary Is arthropod saliva the Achilles’ heel of vector-borne diseases?