Ticks are blood-feeding arthropods that may secrete immunosuppressant molecules, which inhibit host inflammatory and immune responses and provide survival advantages to pathogens at tick bleeding sites in hosts. In the current work, two families of immunoregulatory peptides, hyalomin-A and -B, were first identified from salivary glands of hard tick Hyalomma asiaticum asiaticum. Three copies of hyalomin-A are encoded by an identical gene and released from the same protein precursor. Both hyalomin-A and -B can exert significant anti-inflammatory functions, either by directly inhibiting host secretion of inflammatory factors such as tumor necrosis factor-␣, monocyte chemotectic protein-1, and interferon-␥ or by indirectly increasing the secretion of immunosuppressant cytokine of interleukin-10. Hyalomin-A and -B were both found to potently scavenge free radical in vitro in a rapid manner and inhibited adjuvant-induced inflammation in mouse models in vivo. The JNK/SAPK subgroup of the MAPK signaling pathway was involved in such immunoregulatory functions of hyalomin-A and -B. These results showed that immunoregulatory peptides of tick salivary glands suppress host inflammatory response by modulating cytokine secretion and detoxifying reactive oxygen species.Ticks are parasites that feed on the blood of their hosts. Their salivary glands can secrete various immunomodulatory molecules to inhibit host inflammatory and immune responses (1-7). Ticks are second only to mosquitoes as vectors of disease-causing agents to humans and the most important arthropod capable of transmitting pathogens to other animal species (8 -13). Medically important tick-borne diseases include Lyme disease (14, 15), tick-borne encephalitis, granulocytic ehrlichiosis (16 -19), babesiosis (2, 7, 12), and Crimean-Congo hemorrhagic fever, which occurs sporadically throughout much of Africa, Asia, and Europe and results in an ϳ30% fatality rate (16 -19).Many reports have showed that proteins extracted from saliva and salivary glands of several ticks may inhibit humoral immunity and the B and T cell responses to tick-transmitted pathogens (1, 20 -26) and, furthermore, may facilitate the pathogen transmission and infection to their hosts by downregulating host immunity (27-34), altering blood flow (30,35,36) and inhibiting inflammation (37-41). For example, tick saliva-enhanced transmission has also been demonstrated for several viral and bacterial pathogens, including tick-borne encephalitis virus and Borrelia burgdorferi spp., the causative agent of Lyme disease (11,22,38). It has been suggested that the anti-inflammation mechanism is well conserved among tick species, in spite of the presence of the marked molecular polymorphism in the protein profile of salivary glands from individual ticks (11). Much of the literature has shown that saliva and salivary gland extracts of ticks can inhibit host inflammatory responses by modulating its cytokine secretion or directly blocking cytokine activities via extract-cytokine interactions (1,20,24,26,27,32). ...
