Function and antigenicity of mosquito salivary proteins

Substantially improved knowledge of mosquito salivary repertoires has been achieved in the last decade through transcriptome and expression/functional studies. Nevertheless, a large number of salivary proteins are so far without a function and our understanding of the effects of mosquito saliva on host immune response and pathogen transmission/infection is still rudimentary. We recently characterized two Anopheles gambiae salivary proteins restricted to anopheline mosquitoes and involved in hematophagy: gSG6 and cE5. The first helps mosquito blood feeding by a still unknown mechanism, the second is a highly specific fast- and tight-binding thrombin inhibitor. Both proteins are immunogenic to humans and evoke different humoral responses in exposed individuals from a malaria hyperendemic area. The IgG response to gSG6 decreased with age whereas anti-cE5 IgG levels showed an opposite trend. IgG4 was the dominant anti-gSG6 IgG subclass (IgG4>IgG1), instead IgG1 was the main anti-cE5 antibody (IgG1>>IgG4). Since IgG1 and IgG4 are often considered as markers of Th1- and Th2-type responses we believe we have identified two salivary antigens with strikingly different antigenic properties: (i) gSG6, triggering a Th2-type response, with high IgG4 levels and induction of tolerance; (ii) cE5, eliciting a Th1-type response, with high IgG1 levels and no development of tolerance. The availability of salivary components triggering differential host responses is expected to help dissecting the complexity of the human immune response to mosquito saliva and to provide a deeper understanding of the potential for mosquito salivary proteins to be exploited in the fight against vector-borne diseases.