maxadilan, a PpSP15-related protein, six members of a family of putative anticoagulants, an antigen 5-related protein, a D7-related protein, a cDNA belonging to the Cimex apyrase family of proteins, a protein homologous to a silk protein with amino acid

The New World sand fly, Lutzomyia longipalpis, is an important vector of Leishmania chagasi, causal agent of the visceral form of leishmaniasis in humans. These sand flies, as well as many other blood feeders, contain potent pharmacological components in their saliva that assist them in obtaining their blood meals and evading host inflammatory and immune responses. Components such as anticoagulants, inhibitors of platelet aggregation and vasodilators have been described in blood feeders (Ribeiro, 1987, 1995). In the saliva of Lu. longipalpis, apyrase, anticoagulant, vasodilatory and immunomodulatory activities have been reported; some of these molecules were characterized at the molecular level (Lerner et al., 1991; Charlab et al., 1999; Gillespie et al., 2000). Arthropod saliva modifies the physiology of the host at the site of the bite, making it more permissive for pathogen invasion (Titus and Ribeiro, 1988; Ribeiro, 1989; Kamhawi, 2000; Nuttall et al., 2000). In some vector/parasite systems, immune response to arthropod feeding or arthropod bites (probably to salivary proteins) precludes the establishment of the pathogen in the vertebrate host (Bell et al., 1979; Jones and Nuttall, 1990; Wikel et al., 1997; Nazario et al., 1998; Kamhawi et al., 2000). There are two hypotheses (not mutually exclusive) to explain this protection. First, vertebrate immune response to insect salivary proteins, particularly antibodies, may neutralize the effect of the salivary component(s) responsible for pathogen establishment. There is evidence supporting this hypothesis; Morris et al. (2001) demonstrated that animals vaccinated with maxadilan, a potent vasodilator and immunomodulator from Lu. longipalpis, raised antibodies against this salivary protein, which resulted in animals protected against Le. major infection. Second, vertebrate host immune response to salivary proteins creates an inhospitable environment to the pathogen, which is either killed or its future development negatively affected at the site of the bite. In this case, the anti-salivary immune response may be mainly a cellular rather than humoral response. Evidence to support this hypothesis comes from the work of Kamhawi et al. (2000), where animals pre-exposed to Phlebotomus papatasi sand fly The Journal of Experimental Biology 207, 3717-3729 Published by The Company of Biologists 2004 doi:10.1242/jeb.01185