Humoral Response to the Anopheles gambiae Salivary Protein gSG6: A Serological Indicator of Exposure to Afrotropical Malaria Vectors

Abstract

Salivary proteins injected by blood feeding arthropods into their hosts evoke a saliva-specific humoral response which can be useful to evaluate exposure to bites of disease vectors. However, saliva of hematophagous arthropods is a complex cocktail of bioactive factors and its use in immunoassays can be misleading because of potential cross-reactivity to other antigens. Toward the development of a serological marker of exposure to Afrotropical malaria vectors we expressed the Anopheles gambiae gSG6, a small anopheline-specific salivary protein, and we measured the anti-gSG6 IgG response in individuals from a malaria hyperendemic area of Burkina Faso, West Africa. The gSG6 protein was immunogenic and anti-gSG6 IgG levels and/or prevalence increased in exposed individuals during the malaria transmission/rainy season. Moreover, this response dropped during the intervening low transmission/dry season, suggesting it is sensitive enough to detect variation in vector density. Members of the Fulani ethnic group showed higher anti-gSG6 IgG response as compared to Mossi, a result consistent with the stronger immune reactivity reported in this group. Remarkably, anti-gSG6 IgG levels among responders were high in children and gradually declined with age. This unusual pattern, opposite to the one observed with Plasmodium antigens, is compatible with a progressive desensitization to mosquito saliva and may be linked to the continued exposure to bites of anopheline mosquitoes. Overall, the humoral anti-gSG6 IgG response appears a reliable serological indicator of exposure to bites of the main African malaria vectors (An. gambiae, Anopheles arabiensis and, possibly, Anopheles funestus) and it may be exploited for malaria epidemiological studies, development of risk maps and evaluation of anti-vector measures. In addition, the gSG6 protein may represent a powerful model system to get a deeper understanding of molecular and cellular mechanisms underlying the immune tolerance and progressive desensitization to insect salivary allergens.

Purification of Plasmodium Sporozoites Enhances Parasite-Specific CD8 + T Cell Responses

“…It is tempting to postulate that APCs could be overwhelmed with mosquito-derived peptides, leading to mosquito-specific responses that self-regulate antigen-presenting DCs even as these APCs simultaneously present smaller quantities of parasite-derived antigens. Mosquito-derived antigens are known to induce antibody responses (54)(55)(56)(57), and both saliva and sporozoites remain in the skin for up to 18 h postbite (58).…”

A draft genome sequence of an invasive mosquito: an ItalianAedes albopictus

“…The availability of the complete salivary repertoire of A. albopictus will allow further functional studies and may help in developing reliable serological tools to evaluate human exposure to Aedes arboviral vectors, as previously done for Anopheles malaria vectors. 86,87 miRNA-encoding genes The class of microRNAs (miRNAs) contains small, 22-23 nt long molecules that have been found to play crucial roles in regulating gene expression both in plants and metazoans. Several papers have dealt with the characterisation of miRNAs in mosquitoes, including A. albopictus.…”

Immunological consequences of arthropod vector‐derived salivary factors

“…Despite the small size of the inoculum and the fact that only minute amounts of saliva enter the host, the impact is significant as evidenced by the induction of antibody responses against saliva proteins. Although, in the specific case of mosquitoes, a few of the saliva proteins are indeed immunogenic, the resulting antibody response directly correlates with the number of mosquito bites, thus representing a useful biomarker for exposure to (potentially infectious) bites [13,14]. Although studies with West Nile Virus reveal that the mortality of mice correlates with the number of prior exposures to the mosquito [15], the successful induction of antibodies to certain saliva proteins, which neutralize their function, can protect the vertebrate host from the infection by a subsequent bite from the same vector species.…”