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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.
Highlights
It is well known that blood sucking arthropods salivate injecting into their hosts, while feeding, a complex cocktail of bioactive factors of essential importance for the successful acquisition of the blood meal [1]
The purity and correct refolding of the recombinant gSG6 was confirmed by reverse-phase high-pressure liquid chromatography (RP-HPLC) and mass spectrometry (MS) (Figure 1, panels D–E)
The gold standard classical method for the assessment of malaria transmission intensity is the determination of the entomological inoculation rate (EIR), which measures human exposure to parasite-carrying mosquitoes
Summary
It is well known that blood sucking arthropods salivate injecting into their hosts, while feeding, a complex cocktail of bioactive factors of essential importance for the successful acquisition of the blood meal [1]. The main role of these components is to antagonize the physiological responses of the host to tissue injury, namely hemostasis, inflammation and immunity [2,3] Independently from their biochemical properties, these factors elicit into the host a humoral response and, circulating antisalivary proteins antibodies can be detected in the sera of individuals repeatedly bitten by arthropods. Comparative analysis of sialotranscriptomes from different Culicidae family members allowed for the identification of a large group of Anopheles-specific proteins, i.e. not found in Culex or Aedes mosquitoes, and viceversa [17,18,19] These proteins, if immunogenic, may represent ideal candidates for the development of serological markers of exposure to anopheline mosquitoes
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